Dr. Cuevas-Navarro’s [Berger Foundation Fellow] research project focuses on targeting mutations in the RAS genes (HRAS, NRAS, and KRAS), present in about 30% of cancer patients and notorious for driving aggressive tumor growth. Dr. Cuevas-Navarro aims to mitigate these mutations’ effects by using pharmacological agents to enhance a biochemical process that regulates RAS proteins. His project will investigate the mechanism of action of these compounds and assess their effectiveness in patient-derived cancer models. This research has the potential to expand treatment options across various cancer types, including those where current treatments are limited. Dr. Cuevas-Navarro received his PhD from University of California, San Francisco and his BS from University of California, Davis.
All Cancers
Current ProjectsT cell therapies have led to promising results in treating blood cancers, but new approaches are required to translate these results to solid tumors. In solid tumors, T cells face unique challenges in the tumor microenvironment (TME), which limits the persistence and efficacy of adoptive T cell therapies. In T cell lymphomas (TCLs), tumor cells overcome many of the same challenges through acquired mutations. Fueled by natural selection, tumor mutations produce novel and elegant solutions to address T cell deficits in the TME. Understanding that these modifications may be superior to current bioengineering capabilities, Dr. Devany [Bakewell Foundation Fellow] plans to introduce gain-of-function mutations into therapeutic T cells to grant them the ability to survive, proliferate, and function in the TME. He will determine how each mutation restores different aspects of T cell function, allowing for the design of combinations of mutations that act synergistically. His results will aid in the development of next-generation T cell therapies to cure solid tumors. Dr. Devany received his PhD from University of Chicago, Chicago and his BS from University of California, Santa Barbara.
Global increases in metabolic syndrome, obesity, and diabetes are likely related to the overconsumption of hyper-palatable, cheap, ultra-processed food containing high amounts of added sugar and fat. Intriguingly, the vagus nerve has been discovered as the key conduit relaying information about sugar or fat ingestion from the gut to the brain, where a preference for sugar or fat is then developed and reinforced. Dr. Du [HHMI Fellow] aims to understand how the neurons are organized in the gut-brain vagal axis to sense sugar and fat, and to identify and characterize the neural circuits downstream of the gut-brain vagal axis that produce an insatiable appetite for sugar and fat. Understanding the basic biology of the gut-brain axis can provide important insights and strategies to help combat overconsumption of highly processed foods rich in sugar and fat, which may contribute to lowering the risk of metabolic diseases and cancer. Dr. Du received his PhD from The University of Texas Southwestern Medical Center, Dallas and his BS from the Tsinghua University, Beijing.
Courtney Ellison, PhD [Marilyn and Scott Urdang Breakthrough Scientist] is investigating how single bacterial cells join together to form complex, multicellular structures called biofilms. Biofilms protect bacterial cells from antibiotics and antimicrobial agents, making them difficult to eliminate. Some biofilm-forming species may cause certain cancers, and biofilms of infectious bacteria threaten immunocompromised patients such as those undergoing chemotherapy. Dr. Ellison focuses on bacterial appendages called type IV pili that play a crucial role in biofilm formation. Understanding the role of pili and their contribution to biofilm progression may lead to novel therapies to eliminate biofilms.
Dr. Gao [The Mark Foundation for Cancer Research Fellow] studies how the tumor microenvironment influences anti-tumor immune responses. Her research focuses on lipid metabolism in cytotoxic T lymphocytes (CTLs), a specialized population of white blood cells that kill malignant cells. To defend against this attack, tumors release lipid metabolites that can incapacitate infiltrating CTLs. Consequently, these metabolites create an immunosuppressive environment and promote tumor progression. Dr. Gao aims to unravel the pathways utilized by these harmful lipids. She is also investigating whether modifying lipid metabolism in immune cells can unleash CTL response and accelerate tumor shrinking. These studies have the potential to identify new therapeutic targets that will improve immunotherapy.
Dr. Greenberg [HHMI Fellow] is focusing on how sensory neurons that innervate internal organs develop and function under changing environmental conditions. Our ability to sense and respond to fluctuations in blood-oxygen levels or exposure to gastric irritation is controlled by sensory neurons from the vagus nerve or the dorsal root ganglia. These neurons detect changes in numerous organs including those critical to reproduction, and mediate responses. Understanding how sensory neurons respond to these microenvironments may provide new insights into how certain conditions contribute to tumor growth and identify targets for the development of cancer therapies.
Interoceptive neural circuits are responsible for sensing internal changes in the body and initiating appropriate responses. In the context of female reproduction, these neurons sense internal states within the reproductive tract and maintain homeostasis by modulating functions like smooth muscle contractions, fluid flow, and communication with the central nervous system. The female reproductive tract undergoes major changes throughout life, ranging from pregnancy to gynecological cancers like high-grade ovarian carcinoma. Dr. Greenberg is investigating how interoceptive neurons monitor the female reproductive tract and modulate essential physiologies in these changing hormonal and biological states. Her research on the typical functions of reproductive neurons and on the neuronal contribution to tumor progression may suggest novel therapeutic approaches for gynecological cancer treatment.
A unifying hallmark of several types of cancer is the uncontrolled fragmentation of mitochondria, the microscopic compartments that generate energy for the cell. Although many key players have been implicated in this process, the manner in which these factors assemble to modify the mitochondrial architecture and induce the unrestricted fragmentation associated with cancer is unknown. Dr. Grotjahn [Nadia's Gift Foundation Innovator] uses cutting-edge instrumentation, powerful electron microscopes, and pioneering image processing techniques to visualize this process inside cancer cells. Her work has the potential to identify new targets to block mitochondrial fragmentation as a future therapeutic strategy to prevent cancerous cell proliferation and tumor growth.
Dr. Grunwald [Lallage Feazel Wall Fellow] focuses on the disconnect between genotype and phenotype. Despite our wealth of knowledge about the human genome, we are often unable to accurately predict which individuals will suffer from genetic diseases, including cancers. It has been proposed that cells have mechanisms capable of buffering genetic variation, such that the phenotypic outcome of these genetic variants is sometimes obscured. When buffering systems, or “capacitors,” are de-stabilized or overwhelmed by genetic or environmental factors, “cryptic” genetic variants are exposed. Understanding the mechanism by which organisms buffer accumulated cryptic variants may illuminate the evolution of complex traits while providing vital insight into the heritability of genetic disease.
Regulation of gene transcription is a major mechanism cells use to modify the levels of certain proteins in response to their environment. A specific class of genes called immediate-early genes (IEGs) responds rapidly to external stimuli to adjust downstream gene transcription programs before any new proteins are synthesized. Abnormal expression of IEGs has been implicated in multiple types of cancers, as well as in neurological syndromes like addiction. Despite extensive study, the regulation of IEGs remains poorly understood. Dr. Gu’s work focuses on revealing the molecular mechanisms of IEG expression in cells and establishing model systems to study the physiological and disease-related outcomes caused by misregulation of this process. Dr. Gu [National Mah Jongg League Fellow] received her PhD from MIT and her BSc from Peking University.