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Here are some of the biggest medical advances in 2023.

New treatments include the first CRISPR gene-editing therapy, an Alzheimer’s drug and RSV vaccines

In March, the U.S. Food and Drug Administration said the nasal spray Narcan, which can reverse the effects of an opioid overdose, could be sold over the counter.

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By Erin Wayman

December 14, 2023 at 7:00 am

Weight-loss drugs stole much of the spotlight in 2023, but these medical advances treating other conditions are also worthy of attention ( SN: 12/13/23 ).

Green light for CRISPR gene editing

On December 8, the U.S. Food and Drug Administration approved the world’s first CRISPR/Cas9 gene-editing therapy ( SN: 12/8/23 ). The treatment, called Casgevy, targets sickle cell disease by helping patients produce healthy hemoglobin. In people with the disease, hemoglobin is abnormal, causing red blood cells to become hard and crescent shaped, which can block blood flow. By March 2024, the FDA will decide whether the same therapy can be used to treat beta-thalassemia, a disorder that reduces hemoglobin production.

Slowing down Alzheimer’s

The Alzheimer’s drug lecanemab (brand name Leqembi) won full FDA approval in July. Like the drug aducanumab approved in 2021, lecanemab removes the amyloid plaques that build up in the brains of people with Alzheimer’s. The drug doesn’t stop the disease, but in a clinical trial, lecanemab slowed cognitive decline by about 30 percent over 18 months compared with a placebo ( SN: 8/12/23, p. 9 ).

A gene therapy for muscular dystrophy

In June, the FDA approved the first gene therapy for children with Duchenne muscular dystrophy. Due to a faulty gene, people with this muscle-wasting disease don’t make the protein dystrophin, which helps keep muscle cells intact. The therapy helps the body produce a version of the missing protein ( SN: 6/22/23 ).

Guarding against RSV

Several ways to protect against respiratory syncytial virus arrived this year. In May, the FDA approved the first RSV vaccine, called Arexvy, in the United States , for adults age 60 and older ( SN: 6/17/23, p. 8 ), and then in August, a vaccine for pregnant people , called Abrysvo ( SN: 8/25/23 ). A monoclonal antibody — a lab-made antibody that mimics immune system proteins — won approval in July to protect children 2 and younger from the virus, which sends as many as 80,000 young children to U.S. hospitals each year (S N: 4/27/23 ). But in October, limited supplies of the therapy led the U.S. Centers for Disease Control and Prevention to recommend reserving it for babies at highest risk for complications from RSV.

A pill for postpartum depression

Until August, the only medication in the United States specifically targeting postpartum depression required a 60-hour intravenous infusion in a hospital ( SN: 3/22/19 ). With FDA approval of zuranolone (brand name Zurzuvae), those afflicted with postpartum depression can take an oral medication at home and experience improvement in as little as three days .

Birth control, no prescription required

In July, the FDA ruled that the oral contraceptive norgestrel, first approved in 1973, be available without a prescription. It’s the first OTC daily birth control pill in the United States. Some public health experts argue that reducing barriers to contraception is especially important to reproductive autonomy now that state bans have limited access to abortion ( SN: 5/19/23 ).

A shot against chikungunya

The chikungunya virus can cause fever and severe joint pain, and be fatal to newborns. In November, the FDA approved the first vaccine against the virus , which is transmitted by mosquitoes. The virus is most prevalent in tropical regions, but the FDA warns that it’s spreading to new parts of the globe.

Narcan over the counter

The nasal spray Narcan, aka naloxone, can reverse the effects of an opioid overdose within minutes. In March, the FDA ruled this life-saving drug can be sold over the counter . Officials hope that easier access to Narcan can help fight the opioid epidemic, which claimed the lives of nearly 645,000 people from 1999 to 2021 due to overdoses.

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Nih research matters.

December 21, 2023

2023 NIH Research Highlights - Promising Medical Findings

Results with potential for enhancing human health.

With NIH support, scientists across the United States and around the world conduct wide-ranging research to discover ways to enhance health, lengthen life and reduce illness and disability. Groundbreaking NIH-funded research often receives top scientific honors. In 2023, these honors included  two NIH-supported scientists who received Nobel Prizes . Here’s just a small sample of the NIH-supported research accomplishments in 2023. Also see this year's  Human Health Advances  and  Basic Research Insights .

Printer-friendly version of full 2023 NIH Research Highlights

Immune and hormonal features of Long COVID

About one in eight people who survive an acute SARS-CoV-2 infection go on to have persistent symptoms. The processes that give rise to this syndrome, known as Long COVID, remain unclear. Researchers found several immune and hormonal differences between people with Long COVID and those without. Another study found that infection with a common cold virus may predispose some people to develop Long COVID . This year, researchers also discovered how COVID-19 may damage cells’ energy production and potentially cause some symptoms of Long COVID.

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Protein may be linked to exercise intolerance in ME/CFS

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) live with debilitating symptoms. These including exhaustion, exercise intolerance, cognitive problems and worsening of symptoms after even mild exertion. A study suggested that high levels of a protein called WASF3 may reduce energy production in the muscle cells of people with ME/CFS. Blocking this protein in cells in the laboratory restored energy production, suggesting a potential new strategy for treating the condition.

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Engineering skin grafts for complex body parts

Advances in bioengineering have allowed researchers to grow new patches of skin in the lab. But these skin patches have been small and limited in shape. Using new techniques, scientists grew strong skin in the shape of a full human hand. This technology has the potential to help heal burns and other damage to complex body parts with less trauma and scarring.

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Blood test for early Alzheimer’s detection

One of the first stages of Alzheimer’s disease involves the formation of toxic aggregates of a protein called amyloid beta (Aβ). The ability to detect these early would let scientists test new treatments before irreparable brain damage occurs. Researchers developed a blood test that could detect the toxic Aβ aggregates before Alzheimer’s symptoms appeared. This is one of several promising approaches to early diagnosis of Alzheimer’s and other dementias.

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Erythritol and cardiovascular events

Artificial sweeteners can help people reduce their sugar and calorie intake. But little is known about the long-term health consequences. Researchers found that elevated blood levels of the artificial sweetener erythritol were associated with increased risk of heart attack and stroke. When used as a sweetener, erythritol is typically added at levels more than 1,000-fold higher than those found naturally in foods. The results highlight the need to further study erythritol’s long-term effects on cardiovascular health.

Read more 2023 NIH Research Highlights: Basic Research Insights

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FDA Approves and Authorizes Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants

FDA News Release

Today, the U.S. Food and Drug Administration approved and granted emergency use authorization (EUA) for updated mRNA COVID-19 vaccines (2024-2025 formula) to include a monovalent (single) component that corresponds to the Omicron variant KP.2 strain of SARS-CoV-2. The mRNA COVID-19 vaccines have been updated with this formula to more closely target currently circulating variants and provide better protection against serious consequences of COVID-19, including hospitalization and death. Today’s actions relate to updated mRNA COVID-19 vaccines manufactured by ModernaTX Inc. and Pfizer Inc.

In early June, the FDA advised manufacturers of licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 formula) should be monovalent JN.1 vaccines. Based on the further evolution of SARS-CoV-2 and a rise in cases of COVID-19, the agency subsequently determined and advised manufacturers that the preferred JN.1-lineage for the COVID-19 vaccines (2024-2025 formula) is the KP.2 strain, if feasible.

“Vaccination continues to be the cornerstone of COVID-19 prevention,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “These updated vaccines meet the agency’s rigorous, scientific standards for safety, effectiveness, and manufacturing quality. Given waning immunity of the population from previous exposure to the virus and from prior vaccination, we strongly encourage those who are eligible to consider receiving an updated COVID-19 vaccine to provide better protection against currently circulating variants.”

The updated mRNA COVID-19 vaccines include Comirnaty and Spikevax, both of which are approved for individuals 12 years of age and older, and the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, both of which are authorized for emergency use for individuals 6 months through 11 years of age.

What You Need to Know

• Unvaccinated individuals 6 months through 4 years of age are eligible to receive three doses of the updated, authorized Pfizer-BioNTech COVID-19 Vaccine or two doses of the updated, authorized Moderna COVID-19 Vaccine.
• Individuals 6 months through 4 years of age who have previously been vaccinated against COVID-19 are eligible to receive one or two doses of the updated, authorized Moderna or Pfizer-BioNTech COVID-19 vaccines (timing and number of doses to administer depends on the previous COVID-19 vaccine received).
• Individuals 5 years through 11 years of age regardless of previous vaccination are eligible to receive a single dose of the updated, authorized Moderna or Pfizer-BioNTech COVID-19 vaccines; if previously vaccinated, the dose is administered at least 2 months after the last dose of any COVID-19 vaccine.
• Individuals 12 years of age and older are eligible to receive a single dose of the updated, approved Comirnaty or the updated, approved Spikevax; if previously vaccinated, the dose is administered at least 2 months since the last dose of any COVID-19 vaccine.
• Additional doses are authorized for certain immunocompromised individuals ages 6 months through 11 years of age as described in the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine fact sheets.

Individuals who receive an updated mRNA COVID-19 vaccine may experience similar side effects as those reported by individuals who previously received mRNA COVID-19 vaccines and as described in the respective prescribing information or fact sheets. The updated vaccines are expected to provide protection against COVID-19 caused by the currently circulating variants. Barring the emergence of a markedly more infectious variant of SARS-CoV-2, the FDA anticipates that the composition of COVID-19 vaccines will need to be assessed annually, as occurs for seasonal influenza vaccines.

For today’s approvals and authorizations of the mRNA COVID-19 vaccines, the FDA assessed manufacturing and nonclinical data to support the change to include the 2024-2025 formula in the mRNA COVID-19 vaccines. The updated mRNA vaccines are manufactured using a similar process as previous formulas of these vaccines. The mRNA COVID-19 vaccines have been administered to hundreds of millions of people in the U.S., and the benefits of these vaccines continue to outweigh their risks.

On an ongoing basis, the FDA will review any additional COVID-19 vaccine applications submitted to the agency and take appropriate regulatory action.

The approval of Comirnaty (COVID-19 Vaccine, mRNA) (2024-2025 Formula) was granted to BioNTech Manufacturing GmbH. The EUA amendment for the Pfizer-BioNTech COVID-19 Vaccine (2024-2025 Formula) was issued to Pfizer Inc.

The approval of Spikevax (COVID-19 Vaccine, mRNA) (2024-2025 Formula) was granted to ModernaTX Inc. and the EUA amendment for the Moderna COVID-19 Vaccine (2024-2025 Formula) was issued to ModernaTX Inc.

Related Information

• Comirnaty (COVID-19 Vaccine, mRNA) (2024-2025 Formula)
• Spikevax (COVID-19 Vaccine, mRNA) (2024-2025 Formula)
• Moderna COVID-19 Vaccine (2024-2025 Formula)
• Pfizer-BioNTech COVID-19 Vaccine (2024-2025 Formula)
• FDA Resources for the Fall Respiratory Illness Season
• Updated COVID-19 Vaccines for Use in the United States Beginning in Fall 2024
• June 5, 2024, Meeting of the Vaccines and Related Biological Products Advisory Committee

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products.

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New findings on tuberculosis could change how we treat inflammatory disorders

by Katherine Fenz, Rockefeller University

Tuberculosis (TB) is a confounding scourge. It's the leading cause of death from infectious disease in the world, and yet it's estimated that those deaths represent perhaps 5% of infections with Mycobacterium tuberculosis (Mtb). Antibiotics can take credit for saving the lives of some of those with Mtb, but a chasm nevertheless persists between the prevalence of infection and the targeted severity of its impact. A growing body of evidence suggests genetic vulnerabilities to TB account for that gap.

Now researchers from The Rockefeller University have found another rare mutation that leaves its carriers much more likely to become ill with TB—but, curiously, not with other infectious diseases. This finding, recently published in Nature , may upend long held assumptions about the immune system .

It's long been known that an acquired deficiency of a pro-inflammatory cytokine called TNF is linked to an increased risk of developing TB. The current study, led by Rockefeller's Stéphanie Boisson-Dupuis and Jean-Laurent Casanova, revealed a genetic cause of TNF deficiency, as well as the underlying mechanism: a lack of TNF incapacitates a specific immune process in the lungs, leading to severe—but surprisingly targeted—illness.

The findings suggest that TNF, long considered a key galvanizer of the immune response, might actually play a much narrower role—a discovery with far-reaching clinical implications.

"The past 40 years of scientific literature have attributed a wide variety of pro-inflammatory functions to TNF," says Casanova, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases. "But beyond protecting the lungs against TB, it may have a limited role in inflammation and immunity."

Casanova's lab has been studying the genetic causes of TB for more than two decades through field work in several countries and a wide network of collaborating physicians across the world. They maintain an ever-growing database of whole-exome sequences from a global pool of patients—more than 25,000 people to date. Of those, some 2,000 have had TB.

Over the years they've identified several rare genetic mutations that render some people vulnerable to TB . For example, mutations in a gene called CYBB can disable an immune mechanism called the respiratory burst, which produces chemicals called reactive oxygen species (ROS). Despite its pulmonary-sounding name, the respiratory burst takes place in immune cells throughout the body.

ROS help pathogen-consuming white blood cells called phagocytes (from the Greek for "eating") to destroy the invaders they've devoured. If ROS aren't produced, those pathogens can thrive unchecked, leading to debilitating complications. As a result, carriers of this CYBB mutation become vulnerable to not just TB but to a wide variety of infectious diseases.

For the current study, the team suspected that a similar inborn error of immunity may lay behind the severe, recurring TB infections experienced by two people in Colombia—a 28-year-old woman and her 32-year-old cousin—who had been repeatedly hospitalized with significant lung conditions. In each cycle, they initially responded well to anti-TB antibiotics, but within a year, they were sick again.

Puzzlingly, however, their long-term health records showed that their immune systems functioned normally, and that they were otherwise healthy.

A telling deficiency

To find out why they were particularly prone to getting TB, the researchers performed whole-exome sequencing on the two, as well as a genetic analysis of their respective parents and relatives.

The two were the only members of their extended family with a mutation in the TNF gene, which encodes for proteins linked to the regulation of a variety of biological processes. Short for " tumor necrosis factor ," increased TNF production is also associated with a variety of conditions, including septic shock, cancer, rheumatoid arthritis, and cachexia, which causes dangerous weight loss.

The protein is largely secreted by a type of phagocyte called a macrophage, which relies on the ROS molecules generated by the respiratory burst to finish off pathogens they've consumed.

In these two patients, the TNF gene failed to function, preventing the respiratory burst from occurring, and thus the creation of ROS molecules. As a result, the patients' alveolar macrophages, located in their lungs, were overrun with Mtb.

"We knew that the respiratory burst was important for protecting people against various types of mycobacteria, but now we know that TNF is actually regulating the process," says Boisson-Dupuis. "And when it's missing in alveolar macrophages, people will be susceptible to airborne TB."

She adds, "It's very surprising that the people we studied are adults who have never been sick with other infectious diseases, despite being repeatedly exposed to their microbes. They are apparently selectively at risk for TB."

Treatment potential

The discovery also solves a long-standing mystery about why TNF inhibitors, which are used to treat autoimmune and inflammatory diseases, raise the chances of contracting TB. Without TNF, a key part of the defense against it is defunct.

The findings may lead to a radical reassessment of TNF's role in immune function—and new treatment possibilities.

"TNF is required for immunity against Mtb, but it seems to be redundant for immunity against many other pathogens," Casanova says. "So the question is, what other pro-inflammatory cytokines are doing the jobs we thought TNF was doing? If we can discover that, we may be able to block these cytokines rather than TNF to treat diseases where inflammation plays a role."

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The Emergence of Mpox: Epidemiology and Current Therapeutic Options

Samriddhi ranjan.

1 College of Public Health, George Mason University, 4400 University Drive Fairfax, Fairfax, VA 22030 USA

Kanupriya Vashishth

2 Advance Cardiac Centre Department of Cardiology, PGIMER, Chandigarh, 160012 India

3 NGO Praeventio, Tartu, Estonia

Hardeep Singh Tuli

4 Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207 India

Associated Data

This document includes citations for all the data that were analysed throughout the literature review.

The world recently witnessed the emergence of new epidemic outbreaks like COVID-19 and mpox. The 2022 outbreak of mpox amid COVID-19 presents an intricate situation and requires strategies to combat the status quo. Some of the challenges to controlling an epidemic include present knowledge of the disease, available treatment options, appropriate health infrastructures facilities, current scientific methods, operations concepts, availability of technical staff, financial funds, and lastly international policies to control an epidemic state. These insufficiencies often hinder the control of disease spread and jeopardize the health of countless people. Also, disease outbreaks often put a huge burden on the developing economies. These countries are the worst affected and are immensely dependent on assistance provided from the larger economies to control such outbreaks. The first case of mpox was reported in the 1970s and several outbreaks were detected thereafter in the endemic areas eventually leading to the recent outbreak. Approximately, more than 80,000 individuals were infected, and 110 countries were affected by this outbreak. Yet, no definite vaccines and drugs are available to date. The lack of human clinical trials affected thousands of individuals in availing definite disease management. This paper focuses on the epidemiology of mpox, scientific concepts, and treatment options including future treatment modalities for mpox.

Introduction

Amidst the COVID-19 pandemic, another public health concern emerged as a potential threat to afflict people globally, i.e. an abrupt increase in the incidence of mpox (monkeypox) cases. Indeed, starting from mid-May 2022, cases of human mpox have significantly risen in several non-endemic countries worldwide, leading to the declaration of the ongoing outbreak of mpox as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in July 2022 [ 1 , 2 ]. Mpox disease is caused by the mpox virus (MPXV), a double-stranded DNA virus from the Orthopoxvirus genus, belonging to the Poxviridae family [ 2 , 3 ]. The same genus includes the variola virus, a known causative agent of smallpox [ 2 ]. Genetically, MPXV is identified with two types of clads. Clad I, also known as Congo Basin clad, is mostly clustered in the Central-South Cameroon region till DRC. Infections from this clad are more severe with case fatality rates (CRF) > 10%. Clad II also referred to as West African clad, commonly distributed in western Cameroon to the Sierra Leon area, is further divided into sub-clad groups as IIa and IIb (also now referred to as clad III) having a CRF < 1% [ 4 , 5 ]. Overall reported human case fatality rates (CFRs) range between 3.6 and 10.6% in the endemic regions [ 2 ]. In the current 2022 outbreak, clad IIb was predominant [ 6 , 7 ]. To date, the exact animal reservoir for the mpox virus (MPXV) has remained unknown. However, few native African rodents (Gambian giant rats) and squirrels are suspected to be natural reservoirs of the virus. Common species which were frequently infected with MPXV are squirrels, Gambian giant rats, strip mice, dormice, and primates [ 8 ].

Emergence of Mpox

The first outbreak of mpox was reported in 1958 in a group of 10 captive monkeys at the Statens Seruminstitut, Copehengan, Denmark, and Centre d’Enseignement et de Recherches de Medecine aeronautique, Paris. No human infection was reported in individuals who were in close contact with infected monkeys. Subsequently, the mpox outbreak occurred for the first time in humans between 1970 to 1971 [ 9 ]. The first case was reported in a 9-month-old boy residing in a remote village of the Democratic Republic of Congo (DRC), admitted to a local hospital suspected of smallpox infection. Samples from infected individuals were sent to the WHO Smallpox Reference Center, Moscow, revealing mpox infections in virus isolates [ 10 ]. When inspected from family, monkeys were part of the diet, and their skins were also processed in this area. However, no other cases including secondary infections were reported in the community. Nonetheless, seven more cases were reported during this time period [ 9 ]. The World Health Organization in 1967 took the initiative to collaborate with laboratories to conduct cooperative studies. This was to conduct serological surveys, identify mpox outbreaks, and determine the natural foci of the virus. However, these surveys failed to state any major findings and concluded mpox is not a widespread disease and can exist only in the local environment [ 9 ]. Ever since, there has been a subsequent upsurge of mpox cases, mostly recorded in the DRC province. Approximately, 80% of the cases were reported in this region from the years 1970–1997 [ 11 ]. For the past five decades, DRC is the most affected country with mpox; no other country had reported an mpox outbreak to such an extent [ 12 ].

The initial mpox outbreak that was reported in DRC mostly affected children below 10 years of age. A slight male predominance was observed in the systemic review conducted by Beer and Rao [ 11 ]. Most of the initial outbreaks occurred among individuals living in small rural areas or residing close to humid evergreen tropical forests or individuals commonly involved with bushmeat hunting [ 11 ]. Geographically, the spread of infection from 1970 to 2003 concentrated in the Central and Western parts of Africa (Table 1). Countries which frequently reported infections were Cameroon, the Central African Republic, Gabon, Sierra Leone, Liberia, Nigeria, and Cote d’Ivoire, yet greater outbreaks were mostly detected in DRC [ 13 ]. An active surveillance programme was carried out by WHO between the years 1981 to 1986 reporting total confirmed cases of 338 and 33 deaths, an almost 20 times rise in the reported case after the surveillance [ 10 , 11 ]. A slight drop in the incidence of disease was observed between the period of 1993–1995. But soon after, DRC witnessed a major outbreak from 1996–1997 [ 13 ]. A total of 511 cases were recorded with a surge in secondary transmission rates of up to 78% and a fatality rate between 1 and 5% [ 10 , 13 ].

In 2003, the mpox outbreak occurred for the first time in the USA, outside the African continent. The index case was a 3-year-old girl, bitten by an infected prairie dog, imported from Ghana along with other African rodents to the USA [ 14 ]. A total of 71 cases were reported, including both suspected and laboratory-confirmed cases, as per the CDC report [ 15 ]. During the period of 2005, mpox was registered for the first time in the dry savannah region of Sudan. Overall, 40 cases both suspected and confirmed were recorded. In this outbreak, a change in the genomic structure of MPXV was observed as compared to the MPXV traditionally reported in DRC suggesting the adaptability of MPVX in dry regions from humid evergreen tropical forests [ 10 ]. In the year 2018, mpox travelled for the first time to the UK and was reported in the European continent. Only two cases were registered, in individuals, which had a travel history to Nigeria [ 16 ]. Nevertheless, with the advent of 2022, the world saw a major outbreak of mpox (Table ​ (Table1 1 ).

Decade-wise spread of mpox across different countries between 1970 and 2020 9,10

Mpox Outbreak 2022

Mpox is endemic in Central and West Africa, where hundreds of cases were detected annually for many years, acquired mostly from wild animals and most rarely from infected humans [ 1 , 3 ], which results in a sporadic spillover of cases in humans as observed in the MPVX endemic regions [ 5 ]. However, in the 2022 outbreak of mpox, most of the cases were reported in non-endemic countries like N. America, S. America, and Europe (Fig.  1 ) [ 17 ]. Although the origin of the 2022 outbreak is still unknown, it is highly likely that the initial infection has been imported from an endemic country, allowing the circulation of the virus through close physical contacts among humans [ 1 , 18 ]. For the first time, mpox was documented with transmission chains in countries which had no immediate contact with Central or Western Africa [ 19 , 20 ]. This suggests a probability of undetected MPXV circulating in the local population in the outbreak-hit regions causing disease transmission in humans [ 17 ]. Being a DNA virus, mpox is more stable in nature and may have possibly evolved as a potent virus causing infections in humans in the due course of time [ 17 ]. Daniel et al. reported 6–12 times higher mutation rates in mpox as previously estimated [ 6 ]. Human to human transmissibility of mpox has also evolved in these decades [ 21 , 22 ]. Vertical infection of mpox has been also reported. Pregnant mothers infected with mpox had miscarriages during the first trimester of pregnancy [ 6 ]. Perinatally acquired mpox infection was registered in a 9-day year old neonate as well [ 23 ]. Transmissibility of infection within the family especially from parents to children have also been stated to increase [ 20 , 22 ]. The degree of transmissibility of the diseases, popularly known as R 0 , reported in the 1980 for mpox was 0.83. However, in the 2022 outbreak, the R 0 reported was 1.1–2.4 [ 21 , 24 ]. Pan et al. suggested the increase in the R 0 is due to decreased immunity of individuals due to the absence of smallpox immunization and high contact rates of infection in the MSM community [ 6 ].

Countries reporting mpox historically vs countries reporting an mpox outbreak as recorded in an early March 2023 report by CDC 19

As per the WHO, till 17 March 2023, the total confirmed cases for mpox were 86,601, with 1265 probable cases reported with 112 deaths. Globally, 110 countries were affected by mpox so far (Fig.  2 ) [ 20 ]. Approximately 34.7% of cases were reported in America, the worst affected country [ 20 ]. Majority of the infection occurred through household contacts (43%) and by sexual encounters (43%) [ 20 , 22 ]. Commonly affected individuals were young males who were not vaccinated against smallpox and have had sex with men. There was a slight male predisposition, with the median age reported as 34 years (IQR: 29–41). Around, 98% of individuals who were infected were either gay or bisexual, among which 41% of the people were HIV infected [ 4 ].

Mpox number of cases and deaths recorded in early March 2023 across the continent as per the report by CDC 19

On 23 July 2022, mpox was declared a public health emergency by the Public Health Emergency of International Concern (PHEIC), depicting a risk of international spread, along with significant international coordination to control the disease [ 25 ].

Clinical presentation of this disease includes three distinct phases, i.e. incubation, prodrome, and rash [ 2 ]. The incubation period can last for 3 to 20 days with the median being 7 days followed by the prodrome phase that is characterized by lethargy, myalgia, headache, fever, and lymphadenopathy which may last up to 5 days (Fig.  3 ) [ 2 , 4 , 18 ]. Lymphadenopathy is one of the critical features of the progression of the disease and often reported before the development of skin lesions [ 18 ]. Fever is usually followed by multiple papular, ulcerative, and vesiculopustular skin lesions [ 4 ], which progress from macules to papules, vesicles, pustules, crusts, and lastly scab, presenting for up to 4 weeks [ 2 , 18 ]. In 95% of the cases, skin lesions appears [ 4 ]. Common anatomical sites for skin lesions were anogenital with approximately 73% of cases followed by trunk, arms or legs, face, and eventually palms and soles, only accounting for 10% of the cases. Lesions developed contain infectious virus particles, through which the infection can be transmitted directly with human contacts [ 2 ]. Secondary complications include pneumonia, encephalitis, keratitis, gastroenteritis, sepsis, and secondary bacterial infections, affecting mostly patients with a previous diagnosis of HIV infection [ 2 , 4 , 5 ].

Common features reported in mpox infection 4

Current Treatment Modalities and Prevention

The strategy for the prevention and treatment of mpox is very similar to the treatment of Orthomyxovirus infection [ 26 ]. The 2022 outbreak revealed the urgency to control the spread of mpox as it has caused a potential threat in many countries [ 27 ]. Presently, there is no definitive cure for mpox infection, mild symptoms are manageable, and further complications can be avoided in patients with mpox with the help of supportive care [ 28 , 29 ]. Studies have depicted that patients with mild symptoms recover without any treatment [ 30 – 32 ]. Treatment options available for smallpox are also effective in the treatment of mpox, as the clinical presentation of mpox and smallpox is very similar. These include the vaccinia vaccine, vaccinia immune globulin (IVG), and antiviral agents such as cidofovir, tecovirimat, and brincidofovir [ 32 ]. Furthermore, CDC recommends the use of the potential treatment options should be done depending upon the severity of the cases and for serious emergency cases, as the current drugs pose severe adverse effects, and their therapeutic efficacy is still uncertain [ 33 ]. Antiviral drugs are a choice of treatment in immunocompromised patients, in patients with complicated lesions, in pregnant women infected with mpox, in breast-feeding women, and in the paediatric population [ 34 ]. Tecovirimat is the first line of action antiviral recommended for the treatment of smallpox; it works by inhibiting the viral envelope protein, thereby blocking the final steps of virus maturation and release from infected cells, inhibiting the spread. As per the CDC guidelines, emergency access use of tecovirimat is allowed for compassionate use, for the treatment of Orthopoxvirus infections, such as mpox [ 35 , 36 ]. Cidofovir and its oral analogue brincidofovir are commonly approved drugs for the treatment of smallpox; both act by inhibiting viral DNA polymerase. Different studies have evaluated the effect of brincidofovir against Orthopoxvirus infections [ 37 ]. Studies done by Lanier et al. and others on the effect of cidofovir and brincidofovir have been evaluated for mpox with some success [ 34 , 37 ]. As per the recommended guidelines by CDC, preexposure smallpox vaccination has been advised for veterinarians, monkeypox contacts, healthcare workers caring for mpox patients, researchers, and field investigators [ 38 ]. Prior immunization with the smallpox vaccine has demonstrated some proven protective effects against mpox due to the cross-protective immunity provided by the smallpox vaccine. Furthermore, the severity of clinical manifestations is also reduced [ 39 ]. Currently, three available smallpox vaccines with the US national stockpile, i.e. JYNNEOSTM, ACAM2000, have been licenced (2007) for smallpox, the most recent being Aventis Pasteur Smallpox Vaccine (APSV) which could be potentially used for mpox on a case-to-case basis, under an investigational new drug (IND) protocol. JYNNEOSTM, a third-generation and live viral vaccine, is produced from the modified vaccinia Ankara-Bavarian Nordic [ 40 – 42 ]. Licenced in 2019, JYNNEOSTM is an attenuated non-replicating orthopoxvirus. It is now indicated for both smallpox and mpox prevention for adults. Further, ACAM2000, a second-generation vaccine constituted of live vaccinia virus, under the emergency access ACAM2000 is allowed for mpox during the outbreak. Researchers have demonstrated that these vaccines can be used as pre- and post-treatment options, i.e. either in preventing the infection and the disease or in ameliorating the infection and disease [ 34 , 43 , 44 ]. Studies have demonstrated that pregnant women, children less than 8 years of age, and immunocompromised patients should be given antiviral treatment than vaccination. These vaccines, although approved, have shown some local and systematic side effects such as fever, muscle pain, vaccinia, abdominal and back pain, fatigue, headache, lymphadenopathy, etc. [ 42 – 44 ]. Researchers have also highlighted the need for maintaining appropriate social barriers such as avoiding close contact with affected individuals, avoiding contact with skin lesions of individuals infected with MPXV, etc. [ 44 – 46 ]. Vaccinia immune globulin intravenous (VIGIV) is a choice of treatment in case of severe infection with mpox, though there is a paucity of data about its effectiveness in treating mpox. VIGIV is also under SNS and can be administered under investigational new drugs held by CDC [ 29 , 30 , 47 – 49 ]. Therefore, the treatment options and the repurposing of vaccines need to be considered on a case-to-case basis depending on the severity of cases and the immune state of patients [ 50 ] (Fig. ​ (Fig.4 4 ).

A Symptoms and B mechanism of action of mpox antiviral therapy: cidofovir, brincidofovir, vaccinia immune globulin, and tecovirimat [ 50 ] 

Key Fundamental Findings of the Narrative Review

Some major key findings related to mpox are as follows: mpox was solely endemic to the region of DRC [ 11 ]. There has been a slow and steady increase in mpox cases which has adapted itself to develop into the current outbreak. Secondly, the 1996–1997 DRC outbreak highlighted the increase in secondary transmission rates of mpox, potentially getting adapted to spread in the human population [ 13 ]. Thirdly, the MPXV had adapted to thrive itself from the humid evergreen regions to the dry savannah region of Sudan, as observed in the 2005 outbreak, thus further demonstrating its environmental adaptability to flourish [ 10 ]. Lastly, international travel and commerce have given a wider chance for the disease to spread as reported in the 2003 and 2018 outbreaks of mpox in the USA and the UK [ 14 , 16 ]. All these above factors have led to the 2022 outbreak of mpox, affecting every continent across the globe (Fig.  5 ).

Global spread of mpox in 2023 outbreak 19

Most of the consistent outbreak guidelines available from WHO or CDC only account for people with a high risk of exposure; these guidelines are based on the best available evidence which is based upon risk–benefit analysis and other factors [ 51 ]. Available drugs for the treatment of choice are also limited and lack evidence-based studies in humans [ 29 , 30 , 48 ]. This depicts an extensive need to increase the sustainable funding option to enhance our understanding of the development of new drugs and vaccines to curtail the spread of mpox.

Implication in Future Research

The environmental, behavioural, and social reasons behind the 2022 mpox outbreak remain unknown to date [ 1 ]. A deeper understanding of mpox genetics and biochemistry is essential to control its outbreak. It is currently unclear how mpox is closely related and linked to the viral strain that is primarily found in western Africa, as well as the potential routes of rapid transmission. To further understand the immune defence mechanisms against MPXV, more research is needed on the human systemic and mucosal immune responses. As DNA viruses are more adept to correct mutations; therefore, it is unlikely that the mpox virus will suddenly change during human transmission [ 24 , 52 ]. It is yet unknown, whether vaccinations and earlier infections have given the population immunity. Additionally, exploratory studies are required to pinpoint the precise mpox virus reservoir, understand how the virus spreads naturally, and determine the causes of the present increase in cases across several nations. Currently, no potent drugs are available and limited evidence-based studies are being conducted for the treatment of mpox [ 29 ]. Most of the available choices of treatment are discussed in this paper (Fig.  6 ). Therefore, it becomes essential to investigate the domain of natural products with antiviral properties. This provides alternative treatment options, to prevent human to human spread of infection and restrict virus amplification in the host organisms. There is a recent increased interest among the scientific community to look into the numerous bioactivities of structurally unrelated natural compounds [ 53 , 54 ]. Plant-derived polyphenol resveratrol has beeb shown to significantly suppress replication of MPXV affecting probably the viral DNA synthesis and inducing a comparable effect to the well-characterized Orthopoxvirus inhibitor, i.e. cytosine-1-β- d -arabinofuranoside (AraC) [ 55 ]. Due to the pleiotropic action of natural compounds and lack of systemic toxicity, plant-derived agents may represent target compounds to be explored in future clinical trials to enrich the drug arsenal against Orthopoxvirus infections. Parallel to this, early detection of infected patients who are potentially capable of transmitting the infection is also crucial, pointing to the need for improved diagnosis (particularly in atypical clinical presentations and asymptomatic cases), and better availability of molecular tests. Besides, such continual efforts of preclinical scientists and pharmaceutical companies, availability of health infrastructures, and medical staff are of critical importance—a situation still aggravated by the ongoing COVID-19 pandemic. A high-risk patient population is possibly in danger of mpox nosocomial transmission and deserves more attention. Therefore, it is crucial to administer the proper supportive care [ 24 ]. Consequently, it is necessary to improve genomic sequencing capabilities to identify the mpox viral clade(s). The primary necessities are to combat the spread of mpox while dealing with the ongoing COVID-19 pandemic and to include suitable and timely information campaigns for people at risk. It is challenging to create an evidence-based classification of drug safety and effectiveness having a brief history of mpox. Further studies on various animal models, which may affect medication exposure, are also encouraged. The focus of larger research should be on identifying the patients who are most at risk for consequences from mpox infection as well as the best timing for initiating and completing antiviral therapy.

Different treatment modalities in mpox

The emergence of new diseases is one of the incessant threats which mankind can face. Persistent interference between the environment and humans creates an opportunity for new infections to evolve. Over 75% of the pathogens, which are newly emerging, are zoonotic in nature [ 56 ]. Several diseases like HIV/AIDS, Nipah, SARS, and Ebola including mpox have recently appeared. International travel and commerce and human behaviour often help disease to spread [ 56 ]. With the first emergence of mpox in 1958, little is still known about its reservoir host and vector of the disease. Despite repeated outbreaks of mpox over the past years, it has failed to gather scientific attention. There is a lack of understanding of mpox transmission dynamics and disease evolution. In the areas endemic to mpox, regular disease surveillance is lacking. This also includes the need to promote funding for capacity building required for surveillance of the disease, research activities, and testing facilities [ 17 , 57 ]. The role of central bodies like the World Health Organization plays a major role in controlling such outbreaks. However, non-compliance to guidelines and regulations by health agencies like WHO severely impacts the control measures [ 25 ]. Boosting vaccine development and effective drug development is essential to prevent future outbreaks. In addition, new plant-derived products could be further developed and can be promoted as they potentially have lesser side effects for mpox treatment.

Abbreviations

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SR, KV, and KS: conceptualization and writing; HST: editing and proofreading. All authors reviewed the manuscript.

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Bioinformatics Methods in Medical Genetics and Genomics

Affiliations.

• 1 The Digital Health Institute, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia.
• 2 Life Sciences Department, Novosibirsk State University, 630090 Novosibirsk, Russia.
• 3 Institute of Cytology and Genetics SB RAS, 630090 Novosibirsk, Russia.
• 4 School of Systems Biology, George Mason University, Fairfax, VA 22030, USA.
• 5 Research Centre for Medical Genetics, 115522 Moscow, Russia.
• 6 La Verne University, La Verne, CA 91750, USA.
• 7 Department of Fundamental Biology and Biotechnology, Siberian Federal University, 660074 Krasnoyarsk, Russia.
• PMID: 32872128
• PMCID: PMC7504073
• DOI: 10.3390/ijms21176224

Medical genomics relies on next-gen sequencing methods to decipher underlying molecular mechanisms of gene expression. This special issue collects materials originally presented at the "Centenary of Human Population Genetics" Conference-2019, in Moscow. Here we present some recent developments in computational methods tested on actual medical genetics problems dissected through genomics, transcriptomics and proteomics data analysis, gene networks, protein-protein interactions and biomedical literature mining. We have selected materials based on systems biology approaches, database mining. These methods and algorithms were discussed at the Digital Medical Forum-2019, organized by I.M. Sechenov First Moscow State Medical University presenting bioinformatics approaches for the drug targets discovery in cancer, its computational support, and digitalization of medical research, as well as at "Systems Biology and Bioinformatics"-2019 (SBB-2019) Young Scientists School in Novosibirsk, Russia. Selected recent advancements discussed at these events in the medical genomics and genetics areas are based on novel bioinformatics tools.

Keywords: bioinformatics; gene expression; genomics; human population genetics; medical genetics.

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Conflict of interest statement

The authors declare no conflict of interest.

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16 promising postdoctoral scientists awarded Damon Runyon Fellowships for cancer research

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The Damon Runyon Cancer Research Foundation has named 16 new Damon Runyon Fellows, exceptional postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators. This prestigious Fellowship encourages the nation's most promising young scientists to pursue careers in cancer research by providing them with independent funding ($300,000 total) to investigate cancer causes, mechanisms, therapies, and prevention.

What is so exciting-;and so challenging-;about being a postdoc is that you're called to take what you know and apply it to a new problem. When you're stepping out into open space like that, it's important to feel that you have a net of support under you. The Damon Runyon Fellowship lets us take that leap." Georgia R. Squyres, PhD., Damon Runyon Fellow 

"We are thrilled to be funding these innovative, young scientists with the brilliance and passion to push boundaries and make breakthroughs. Damon Runyon Fellows are the future leaders of their respective fields," said Yung S. Lie, PhD, President and CEO of Damon Runyon.

Spring 2024 Damon Runyon Fellows

Layla J. Barkal, MD, PhD , with her sponsor Michael A. Fischbach, PhD, at Stanford University School of Medicine, Stanford The bacterium Staphylococcus epidermidis (S. epi) is nearly universally present on human skin, and certain strains are capable of eliciting immune responses that can be redirected against tumor antigens . Dr. Barkal is investigating how to harness the immunomodulatory properties of S. epi to develop a new class of T cell immunotherapy that is potent and tumor antigen-specific, avoiding the systemic side effects associated with current immunotherapies. Specifically, she is using a melanoma model to explore how to modulate T cell production with S. epi and how to use other skin bacteria for synergistic anti-tumor effects. This work will form the foundation for human trials of topical bacteria-based cancer immunotherapy. Dr. Barkal received her MD, PhD from University of Wisconsin-Madison, Madison and her BS from Massachusetts Institute of Technology, Cambridge.

R. Camille Brewer, PhD [HHMI Fellow] , with her sponsor Gregory M. Barton, PhD, at University of California, Berkeley B cells, especially those that target cancer antigens, are crucial for fighting tumors; however, not everyone develops them. Our gut bacteria play a vital role in training B cells to recognize a wider range of threats. Dr. Brewer's research explores how these gut bacteria influence the specificity of B cells, and thus our body's ability to combat tumors. Dr. Brewer's research aims to determine if the "training" of B cells by gut bacteria early in life influences their later responses to vaccines and cancer. This investigation may not only improve our understanding of how gut bacteria shape our immune system, but also pave the way for novel cancer treatments utilizing gut bacteria. Dr. Brewer received her PhD from Stanford University, Stanford and her BS from Massachusetts Institute of Technology, Cambridge.

Michael V. Gormally, MD, PhD [Dennis and Marsha Dammerman Fellow] , with his sponsors Christopher A. Klebanoff, MD, and Michael F. Berger, PhD, at Memorial Sloan Kettering Cancer Center, New York Adoptive cell therapy (ACT) is poised to expand the curative potential of immunotherapy. ACT works by administering T cells that have been genetically engineered to express tumor-specific T cell receptors (TCRs) so that they recognize a particular cancer antigen. Dr. Gormally's work addresses two major challenges that currently limit the effectiveness of ACTs against solid tumors: identifying antigen targets that can be recognized by the immune system, and designing TCRs that target those antigens with exquisite specificity. Dr. Gormally and his colleagues have identified multiple immunogenic antigens derived from cancer-causing mutations and developed a powerful approach to retrieve potent, antigen-specific TCRs from large libraries of blood samples from cancer patients. The goal of these efforts is to identify safe and effective TCRs for clinical application. Dr. Gormally received his PhD from the University of Cambridge, Cambridge, his MD from Yale School of Medicine, New Haven, and his BA from Pomona College, Claremont.

Chaiheon Lee, PhD [Suzanne and Bob Wright Fellow] , with his sponsor Amit Choudhary, PhD, at the Broad Institute (Eli and Edythe L. Broad Institute of MIT and Harvard), Cambridge The immune system has the capability to destroy cancer cells harboring mutated genes. Cells display peptides derived from these mutated genes (i.e., portions of the mutant protein) on a molecule called the major histocompatibility complex I (MHC I), triggering cytotoxic T cells to eliminate the cancer cells. Unfortunately, this surveillance system is weak and often subverted by cancer cells. Dr. Lee aims to enhance the immunogenicity of the MHC I-displayed peptides using haptens, small molecules that elicit an immune response when attached to a larger carrier protein. By empowering the immune system, he envisions that these hapten-protein complexes will enable the repurposing of cancer drugs for which resistance has emerged. Dr. Lee received his PhD and BS from the Ulsan National Institute of Science and Technology, Ulsan.

Expery O. Omollo, PhD [Robert A. Swanson Family Fellow] , with his sponsor Gene-Wei Li, PhD, at Massachusetts Institute of Technology, Cambridge Dr. Omollo studies how bacteria have evolved to achieve precise gene expression using strategically placed transcription terminators. In cancer cells, specific mutations lead to uncontrolled transcription of certain genes, resulting in elevated gene expression that fuels cancer progression. Using bacteria as a model, Dr. Omollo aims to uncover how RNA polymerases in cancer cells evade termination signals to maintain high levels of gene expression, encouraging cancer spread. Dr. Omollo received his PhD from University of Wisconsin-Madison, Madison and his BS from Michigan State University, Lansing.

Sangwoo Park, PhD [Merck Fellow] , with his sponsor Marcela V. Maus, MD, PhD, at Massachusetts General Hospital, Boston One way cancer cells evade immune attack is by constructing a thin material barrier called the glycocalyx on their surface to evade detection and destruction by surveilling immune cells. Tiny changes in the glycocalyx thickness, as small as 10 nanometers, can affect the anti-tumor activity of immune cells, including CAR T cells. Dr. Park's goal is to develop strategies to endow CAR T cells with the ability to penetrate the glycocalyx barrier in solid tumors such as breast cancer and glioblastoma. These strategies will increase the effectiveness of CAR-T cell therapy against solid tumors by overcoming a significant mechanism of immune cell evasion. Dr. Park received his PhD from Cornell University, Ithaca and his BS from Korea Advanced Institute of Science and Technology, Daejeon.

Sarah L. Price, PhD [Merck Fellow] , with her sponsor Eric P. Skaar, PhD, at Vanderbilt University Medical Center, Nashville Emerging evidence implicates the pathogenic bacterium C. difficile as an initiator of colorectal cancer. C. difficile exposure can lead to chronic recurrent disease that is difficult to clear with antibiotics. The generation of spores is a well-studied mechanism used by C. difficile to persist; however, other mechanisms of recurrent infection remain poorly understood. Dr. Price hypothesizes that biofilms may function as reservoirs of C. difficile and aims to elucidate their role in disease relapse. She will employ innovative imaging strategies to visualize the composition and development of C. difficile biofilms in the gastrointestinal tract, with the goal of generating insight that will improve treatments for C. difficile infections and identify strategies to prevent colorectal cancer. Dr. Price received her PhD from University of Louisville, Louisville and her BS from University of Tennessee, Knoxville.

Nalin Ratnayeke, PhD [HHMI Fellow] , with his sponsor Scott W. Lowe, PhD, at Memorial Sloan Kettering Cancer Center, New York Pancreatic cancer is a leading cause of cancer-related deaths. The development of drugs targeting mutant KRAS, the oncogenic driver of most pancreatic cancers, has led to much optimism for improved treatments. However, tumor recurrence driven by heterogeneous cancer cell responses to these drugs remains a major challenge. Some cancer cells die, while surviving cells can halt their proliferation or continue to proliferate in the presence of drug, all of which can occur within the same tumor and dictate the overall response to treatment. Dr. Ratnayeke is studying the mechanisms that underlie these heterogeneous responses using mouse models of pancreatic cancer and single-cell genomics to map cellular states to their drug responses. Understanding these mechanisms will inform combination and precision therapies with mutant KRAS-targeting drugs to tune tumor responses in beneficial directions. Dr. Ratnayeke received his PhD from Stanford University, Stanford and his BS from the University of Texas at Austin, Austin.

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David S. Roberts, PhD [Connie and Bob Lurie Fellow] , with his sponsor Carolyn R. Bertozzi, PhD, at Stanford University, Stanford Cancer immunotherapies have shown remarkable benefits, but many tumors remain unresponsive to existing treatments. The mechanisms cancer cells use to evade immune responses during treatment remain largely unknown. Altered cell surface glycosylation, the process of attaching sugars to cell surface biomolecules, is a hallmark of many human cancers. The interaction between cell surface glycoproteins on immune cells with cancer cells represents a major axis of immune evasion and plays a vital role in how cancer cells suppress immune responses during cancer treatment. Dr. Roberts' research aims to molecularly define cell surface glycosylation and understand the role of glycosylation in driving cancer immunosuppression. This knowledge will be leveraged to illuminate the underlying mechanisms of tumor immune evasion and enable next-generation classes of cancer immunotherapies. Dr. Roberts received his PhD from University of Wisconsin–Madison, Madison and his BS from University of California, San Diego.

Ian J. Roney, PhD [HHMI Fellow] , with his sponsor Michael T. Laub, PhD, at Massachusetts Institute of Technology, Cambridge Bacteria have diverse immune systems to defend themselves against viral invaders, many of which use molecular mechanisms also seen in mammalian immune systems. Dr. Roney studies how bacterial immune systems detect virally compromised cells, and how viruses undermine immune systems to prevent the elimination of virally compromised cells from the population. The goal of his research is to uncover novel mechanisms and principles of immune systems that are found across domains of life. The discoveries resulting from this work will broaden our understanding of how immune systems detect and eliminate compromised cells, like cancer cells, and could help guide development of new immunotherapies. Dr. Roney received his PhD from Harvard University, Cambridge and his MS and BS from University of Ottawa, Ottawa.

Rocío D. M. Saavedra-Peña, PhD [HHMI Fellow] , with her sponsor Stephen D. Liberles, PhD, at Harvard Medical School, Boston Before, during, and after a meal, complex signals in the gut must be communicated to the brain to regulate physiology and behavior. Dr. Saavedra-Peña is researching how sensory neurons in the gut detect mechanical stretch, a potent satiety signal after a meal. Although vagal neurons, the primary component of the parasympathetic nervous system, are known to play a role in gut mechanosensation, the contribution of other neurons and mechanoreceptors are still unclear. Since disruptions in gut-brain communication can lead to obesity, metabolic disorders, and increased cancer risk, identifying the key cellular and molecular players in gut mechanosensation will aid in developing new treatments for metabolic disorders and provide a foundation for investigating the function of these circuits in gastric cancers. Dr. Saavedra-Peña received her PhD and MS from Yale University, New Haven and her BS from the University of Puerto Rico-Mayagüez, Mayagüez.

Yoshiki Sakai, PhD [Rhee Family Fellow] , with his sponsor David Bilder, PhD, at University of California, Berkeley Normally, epithelial tissues, which cover all external body surfaces and line internal cavities, expel unwanted cells to maintain health in a process known as cell extrusion. However, some cancer cells, particularly those with the common RasV12 mutation, manage to avoid extrusion. Using Drosophila (fruit flies) as a model, Dr. Sakai will explore how RasV12-mutant cells manipulate neighboring cells to avoid extrusion. Understanding this process could lead to new ways to prevent cancer cells from escaping the epithelial defense, offering potential new treatments. Dr. Sakai received his PhD and BS from Nagoya University, Nagoya.

Wenzhi Song, PhD [HHMI Fellow] , with her sponsor Elaine Fuchs, PhD, at The Rockefeller University, New York The interaction between cancer cells and their non-malignant neighbors in the tumor microenvironment is critical for cancer progression. While certain types of cellular crosstalk within the tissue safeguard against malignancy, cancer cells are often able to exploit nearby cells to fuel tumor growth. Dr. Song is interested in understanding how the complex cellular communication network in the skin, namely its sensory and immunological components, contributes to the development of cutaneous squamous cell carcinoma, one of the most common skin cancers. Identifying novel neuronal and immunological interactions within the tumor microenvironment has the potential to uncover pathways regulating cancer progression and anti-tumor immunity. Dr. Song received her PhD from Yale University, New Haven and her AB from Bryn Mawr College, Bryn Mawr.

Simon Sretenovic, PhD [Connie and Bob Lurie Fellow] , with his sponsor Lars M. Steinmetz, PhD, at Stanford University School of Medicine, Stanford More than one third of all people will receive a cancer diagnosis at some point in their lifetime. Dr. Sretenovic is using both yeast and human cell lines to model various properties of cancerous cells as complex genetic traits. Combining novel CRISPR genome editing approaches with next-generation sequencing technology, he aims to dissect the intricate relationships between genetic variants, chemical and physical environmental factors, and phenotypic outcomes (i.e., observable characteristics). The goal of his project is to understand the genetic basis for a panel of cancer-related traits to inform the development of anti-cancer treatments. Dr. Sretenovic received his PhD from the University of Maryland, College Park, and his MS and BS from University of Ljubljana, Ljubljana.

Jinchun Wu, PhD [Marion Abbe Fellow] , with her sponsor Don W. Cleveland, PhD, at University of California, San Diego Genome rearrangements have been widely observed in human cancers. Recent whole-genome sequencing data has identified chromothripsis, an event that introduces massive genome rearrangements in only one or a few chromosomes through catastrophic shattering and random reattachment, as one of the most frequent genome rearrangements. Chromothripsis has been associated with poor clinical outcomes in multiple cancers, but the shattering mechanisms that induce chromosome fragmentation remain uncharacterized. Dr. Wu aims to determine the role of cytoplasmic nucleases (enzymes that cleave DNA) in chromosome shattering and genome rearrangement, which will contribute to our understanding of chromothripsis in all cancers. She will extend this project to a mouse model of glioma to determine the effects of candidate nucleases on cancer progression. Dr. Wu received her PhD and BS from Peking University, Beijing.

Cheng Yang, PhD , with his sponsor Christopher J. Chang, PhD, at Princeton University, Princeton Protein oxidation occurs when an amino acid gains an oxygen atom in a post-translational modification. Oxidation of the amino acid methionine plays an important role in cellular regulation, and mutations at methionine sites are known to have pathogenic effects in cancer. However, direct assessment of methionine's oxidation product, methionine sulfoxide, remains underexplored. Dr. Yang aims to develop methionine sulfoxide labeling approaches using light or electricity. With the help of these chemical tools, he will profile and identify methionine sulfoxide sites in pancreatic tumors and study their role in metastasis . Dr. Yang received his PhD from the University of Michigan, Ann Arbor and his BS from Naikai University, Tianjin.

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Medical research articles within Nature

News & Views | 28 August 2024

People who lack the immune protein TNF can still fight infection

The immune-signalling protein TNF has an essential role in inflammatory responses. Two people who were found to have no functional TNF are surprisingly healthy and able to fend off most infections, but are susceptible to tuberculosis.

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Fate induction in CD8 CAR T cells through asymmetric cell division

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Article 11 June 2024 | Open Access

The Space Omics and Medical Atlas (SOMA) and international astronaut biobank

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

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The transplant aims to prolong the the person’s life and provides important lessons for physicians.

Outlook | 29 May 2024

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The 2024 Summer Oncology Research Fellowship Program students pose with Dr. Anat Erdreich-Epstein and Project Associate Daikota Barnett during their poster session.

Medical Students Explore a Future in Research Through the Summer Oncology Research Fellowship Program

For many students, summer break represents an opportunity for relaxation and carefree vacations. But for the medical students taking part in the USC/CHLA Summer Oncology Research Fellowship (SORF) Program , summer means something more.

This program, which has existed for over 45 years and is supported by funding from the National Institutes of Health (NIH) and several donor organizations, welcomes applications from students interested in research who will soon be on their summer vacation between years in medical school. The program’s goals are to interest these students in pursuing a career as a physician-scientist conducting cancer research and to help them achieve that.

Selected students are matched with faculty mentor researchers from Children’s Hospital Los Angeles and the Norris Comprehensive Cancer Center at USC’s Keck School of Medicine according to their research interests and previous experience.

This summer’s cohort of participants just finished the program and have presented the findings from their projects to USC and CHLA faculty in a series of three virtual meetings.

“They really all do amazing work, especially considering that the summer is so short,” says Anat Erdreich-Epstein, MD, PhD , the physician-scientist who leads the Summer Oncology Research Fellowship Program. Dr. Epstein specializes in treating pediatric brain cancers in her clinical work in CHLA’s Cancer and Blood Disease Institute , and conducts research in her lab, the Erdreich-Epstein Laboratory , that focuses on the biology of brain cancers. She understands firsthand the value of having an in-depth understanding of both clinical care and research.

“I truly believe that as smart as physicians are and as smart as scientists are, having somebody with both hats on their head is hugely helpful,” Dr. Epstein explains. “They think differently and bring unique insights, as they are able to speak both languages at the same time.”

A challenging path and a need for mentors

Dr. Epstein explains that the number of physician-scientists in the U.S. is dwindling. It is a challenging career path that becomes more difficult when you don't have helpful mentors. Also, medical students interested in research are often encouraged to pursue clinical, rather than laboratory research. While there are many types of research, and all types are needed to advance and improve medical treatments, one of the main goals of the Summer Oncology Research Fellowship Program is to specifically spark interest in laboratory research. “We're looking for students who have that fire burning in them to pursue science, and they will do everything they can to succeed, especially if you help them.”

This year’s projects were focused on laboratory work, clinical projects, computational biology, and AI. “We have had more laboratory science projects this year than in the past,” Dr. Epstein says. “We had 11 of the 20 students in the program doing hands-on laboratory research, which was really awesome.”

The students’ projects spanned a wide range of unique oncology-related topics. For instance, one project experimented with training an AI model to use scans of patients with cancer and data from molecular analyses to help predict their clinical outcomes more accurately. Another project utilized a zebrafish model to explore the molecular pathways involved in a rare type of childhood cancer that has a novel mutation.

Dr. Epstein found it impossible to pick a favorite. “All the students did an awesome job,” she says. And they want to keep going. After the summer, program participants may continue working on their projects part-time to finish their projects, publish, and present at scientific conferences. Dr. Epstein says that like last year, many of this year’s students are taking advantage of that opportunity. “The fact that the NIH is now supporting this aspect of the program is a huge benefit to the students,” she explains.

Dr. Epstein points out that through this work, program participants and their research mentors end up inspiring each other. She encourages any interested researchers at CHLA to take part in the program as mentors in the future. “I just ran into two of our mentors from this summer and they were so excited to tell me how excellent their students were and how much they appreciated the experience,” she says.

James Amatruda, MD, PhD , Interim Chief of the Division of Pediatric Hematology-Oncology, and Interim Director and Head of Basic and Translational Research in the Cancer and Blood Disease Institute , echoes these sentiments. “I had the privilege of hosting a student in the program for the first time, which was very rewarding for everyone in our lab,” he says. He recently spoke to the SORF participants during a virtual presentation of their work. “I have to thank you all because you inspire us. To really engage in the important questions, to bring your brilliance and talents, and to learn new things—it's a reminder to all of us of what can be done with effort and passion.”

Collaborators in and out of the lab

Dr. Epstein emphasizes that there is much more to the program than just the students’ research projects. They also visit scientific centers of excellence and take part in educational seminars covering topics in career development, research communication, oncology and responsible conduct of research. “This summer, we had a lot of career development seminars in particular, and the students told me how much they appreciated those opportunities,” Dr. Epstein says.

The students also have the chance to meet with faculty, trainees and cancer survivors, and develop their skills in producing scientific reports, creating posters and delivering oral presentations. During the SORF poster session, undergraduates taking part in USC’s Programs in Biomedical and Biological Sciences (PIBBS) program, students involved in CHLA’s Samuels Family Latino and African American High School Internship Program (LA-HIP) led by Mark Frey, PhD , and members of CHLA’s George Donnell Society for Pediatric Scientists were in attendance and had the chance to interact with the poster presenters. “There was a really amazing interaction between all of the various students and it was a great opportunity for peer mentoring,” Dr. Epstein explains. Students in the Summer Oncology Research Fellowship Program later attended the LA-HIP students’ presentations of their work.

Events like the poster session are made possible thanks to Project Associate Daikota Barnett. She works to connect students with their research mentors and organize all of the seminars and excursions for program participants, among other responsibilities.

Barnett feels honored to be a part of making the program happen. “A lot of people don’t know exactly what they want to do or what specialty they want to pursue in their first year of medical school, and I feel like this program really helps them to understand where they want to go,” she says.

Making the most of summer

The students in the program are also committed to supporting each other. Beyond their research, they often organize social activities to spend time with one another. This year’s cohort grew exceptionally close. “This summer’s group of students were not just smart and productive researchers, they also gelled together socially really well,” Dr. Epstein explains. “In the evenings and on weekend, they went to the beach, they organized hikes. They just did things together without being prompted, which was really nice to see.” Dr. Epstein was even invited to join the students for a weekend hike and sushi dinner.

Derek Alpert, President of Concern Foundation, one of the donor organizations that supports the Summer Oncology Research Fellowship Program, also continued his tradition of inviting all of the program’s students to attend the foundation’s annual Block Party. This event was held on the historic backlot of Paramount Studios Hollywood and represented another unique bonding experience for program participants.

Dr. Epstein is thrilled with how successful this summer’s program cohort was. “This has been a remarkable summer,” she said to the program participants after they presented their work. “You’ve done amazing work. You connected as a group socially, which was really wonderful. This is exactly what I would love our summers to look like every year.”

Learn more about the Summer Oncology Research Fellowship (SORF) program.

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