37 Investigators Transforming the Landscape of Biomedical Science

The 37 members of this year’s class of Pew scholars and fellows are researchers dedicated to solving complex biomedical puzzles that could translate into therapies to treat a wide range of medical conditions. On June 14, Pew announced its 2018 biomedical scholars, Latin American fellows, and Pew-Stewart Scholars for Cancer Research. The investigators selected this year join a thriving community of nearly 1,000 biomedical scientists from diverse research backgrounds. The scientists will meet annually with other program participants to discuss their work, and exchange ideas with peers in fields outside of their own.

For nearly 35 years, Pew has channeled creativity in the biomedical sciences through the biomedical scholars, Latin American fellows, and Pew-Stewart Scholars for Cancer Research programs, which award multiyear grants to promising early-career scientists in the United States and Latin America. These scholars and fellows will advance their explorations of biological mechanisms that lay the groundwork for human health and disease.

The 2018 awardees are investigating a wide range of research topics including:

How infections develop

From viruses to microbes, Pew scientists are closely examining the relationship between pathogens and how they infect hosts. Megan Baldridge, M.D., Ph.D. will explore the conditions that allow severe strains of norovirus to evolve. By examining how the chikungunya virus, which is spread through mosquitoes and causes flu-like symptoms in humans, affects immune cells and nervous system components in the brain, Carolina Lucas, Ph.D. will explore the factors that influence the severity of infection. Matthew Daugherty, Ph.D. will investigate how host cells evolve resistance to infections and how pathogens can in turn counter these defenses. John Karijolich, Ph.D. will explore how DNA sequences known as retrotransposons may help initiate immune system responses to infections, and M. Eugenia Dieterle, Ph.D. will define the mechanisms by which a deadly form of hantavirus enters cells in the lungs.  

Ilana Brito, Ph.D.will look at how antibiotics drive the emergence of multi-drug resistant microbes, while Seth Rakoff-Nahoum, M.D., Ph.D. will examine factors that shape the makeup of microbes living in the gut. To understand how certain microorganisms persevere in harsh conditions, Paul Sigala, Ph.D. will probe the biochemical pathways that allow malarial parasites to survive inside red blood cells. Hesper Rego, Ph.D. will study how the microbe that causes tuberculosis slows down its metabolic activity to evade the effects of antibiotics. Findings from this research could lead to innovative strategies to combat antibiotic resistance and treat the spread of emerging microbial and viral diseases.

Structure and function of cells and tissues

A look inside cells and tissues can reveal the inner workings of a complex, but organized, system, where each component has a purpose and function. Using fine-imaging techniques, Gregory Alushin, Ph.D. will investigate how cells sense and respond to mechanical forces. Francesca Burgos, Ph.D. will examine how linear RNA molecules fold into a specific three-dimensional shape as they are being made, while Aashish Manglik, M.D., Ph.D.will study how information is conveyed by the Hedgehog signaling cascade, a key pathway in embryonic development. Rebecca Voorhees, Ph.D. will explore factors involved in regulating the assembly and degradation of protein complexes, a process cancer cells are particularly dependent on to stay alive. Maria Fernanda Forni, Ph.D. will investigate how cutting calories affects the structure of the skin and hair. Work from these researchers will illuminate the intricate components of cells and tissues that drive biological processes and how medicine might better control cellular pathways compromised by disease.

Immune system and cancer

The immune system not only guards against invading organisms, but also plays key roles in the development of cancer. Anna Beaudin, Ph.D.and Tiffany Reese, Ph.D. are investigating how maternal inflammation alters the risk for autoimmune disorders and the offspring’s susceptibility to viruses later in life, respectively. Enfu Hui, Ph.D. will dissect the mechanism by which the immune system can be boosted to eradicate cancers, and Michael Birnbaum, Ph.D. will study ways to engineer T cells, which are white blood cells that are a part of the immune system, to more effectively recognize and target cancer cells for destruction. Using a newly developed technology, Aaron Ring, M.D., Ph.D. will examine the body’s natural antibody response to immunotherapy in patients with melanoma. Research by this group of scientists could lead to insights into autoimmune diseases—conditions where the immune system attacks a person’s healthy cells—what makes some more susceptible to viruses than others, and improved treatment outcomes in cancer patients.

Spread of cancer

Metastasis is often the last step of cancer progression, where cells from the primary tumor site have broken away to form a new tumor in a different region of the body. Once cancer starts to spread, it is difficult to predict where and how it will take root and therefore to accurately treat it. Adrienne Boire, M.D., Ph.D. will look at genes that are activated in leptomeningeal metastases, a debilitating condition that occurs when cancer cells invade the spinal fluid. Alex Shalek, Ph.D. will also study this condition to characterize cancerous and noncancerous cells in the spinal fluid and determine how the tumor and its environment respond to treatment with immunotherapy. To learn more about how the disease adapts to different conditions as it spreads through the body, Kivanc Birsoy, Ph.D. will study metabolic changes in cancer cells during tumor formation and metastasis. Work in this area could provide new information on how to stop cancer before it spreads and ways to target the disease when it does.

Gene control

Several scholars and fellows from the 2018 class are looking at factors that influence the way genes are turned on or off. Angela Brooks, Ph.D. will investigate how RNA is processed before functional proteins are produced, and the result when this mechanism becomes dysregulated in cancer cells. Similarly, Amy Lee, Ph.D.will look into the role of an RNA-binding protein complex in regulating the production of specific proteins, as well as its connection to abnormal cell growth and proliferation. Grisel Cruz Becerra, Ph.D. will explore the role that structures called prenucleosomes play in regulating gene activity, and Hugo Sepúlveda, Ph.D. will probe how gene-regulatory proteins known as TETs influence the formation of specialized cell types by dictating protein expression. Lastly, Hosea Nelson, Ph.D. will develop artificial systems that perform chemical reactions inside of cells, as a result of gene activation.

Senses and neurobiology

Several researchers in this year’s class are exploring the ways the human brain processes external cues and how the body interprets and responds to these signals. Hiroyuki Kato, Ph.D. will study how animals process sounds and the behavior elicited by different calls. To learn more about the sense of smell, Saket Navlakha, Ph.D. will study how collections of molecules, cells, and organisms process information to solve computational problems, such as how we differentiate between odors. Diego Alvarez, Ph.D. will study the molecular and genetic mechanisms that guide the development of visual circuits after birth. 

To explore the mechanism of decision-making, Nuo Li, Ph.D. will investigate how multiple parts of the brain cooperate to guide decisions based on short-term memory, while Erin Rich, M.D., Ph.D. will investigate the region of the brain that processes expectation, and how our brains adjust decisions when situations change. Victor Cornejo, Ph.D. will explore how the small spines that protrude from a neuron’s dendritic branches handle transmission of electrical signals, while Daniela Di Bella, Ph.D. will look for molecular clues that indicate how neurons in the brain make connections with particular locations in the spinal cord. Finally, Dolores Irala, Ph.D. will examine how non-neuronal cells in the brain regulate the formation of inhibitory connections between neurons. By studying how information is processed and transmitted in the nervous system, this group of researchers hopes to inform new therapies to prevent cognitive decline and boost brain function.

Members of this year’s class are also exploring the underlying mechanisms in neurodegenerative disorders and brain injury. José Rodriguez, Ph.D. will study the structure of toxic prion aggregates, a form of infectious protein that causes disorders such as Creutzfeldt-Jakob disease. Kassandra Ori-McKenney, Ph.D. will investigate the molecular events and proteins driving the development of dementia from traumatic brain injury.