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 airway irritants is controlled by the sensory neurons that comprise the vagus nerve. These neurons detect changes in numerous organs including the heart and lungs, and mediate responses. Understanding how vagal 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.

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.

Dr. Gu [Fraternal Order of Eagles Fellow] is deciphering the combinatorial code of mammalian transcription regulation. The precise and robust regulation of gene expression is typically achieved through a combination of multiple transcription factors. However, we lack understanding of how a mammalian transcription system perceives, processes, and presents combinations of transcription factors. Dr. Gu will combine quantitative modeling and synthetic approaches to analyze the complex interactions among natural transcription regulatory proteins and apply the principles learned to engineer a programmable transcriptional platform with tunable logic. This work promises to deepen our understanding of mammalian transcription regulation and unlock new capabilities for emerging cell-based therapeutics.

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.

Dr. Han [Fayez Sarofim Fellow] is developing novel methodologies to fine-tune cellular signaling pathways that may prevent tumor formation and promote regeneration through the Hedgehog pathway. This pathway plays a central role in regulating embryonic tissue patterning and postnatal tissue renewal. Dr. Han will take an interdisciplinary approach combining chemical biology, protein engineering, and computational modeling to examine the Hedgehog pathway in a cell-type specific and spatiotemporally resolved manner. This work aims to provide mechanistic insights into the function of Hedgehog signaling in tissue repair and establish new therapeutic approaches for regenerative medicine.

Dr. Hananya [Robert Black Fellow] is investigating a component of the DNA repair machinery termed protein ADP-ribosylation. Our cells are constantly exposed to chemicals and electromagnetic radiation harmful to DNA. Since the integrity of our genetic material is critical, cells have evolved a variety of mechanisms to repair lesions in the DNA. But defects in these DNA repair pathways caused by genetic mutations can lead to genomic instability, which drives cancer development. Dr. Hananya is utilizing chemical biology to study ADP-ribosylation and to delineate its role in DNA repair. The research will provide vital information regarding cancer genesis and progression and will contribute to the development of new therapies.

DNA stores the information for making all the proteins in an organism. Transfer RNA (tRNA) plays a key role in building the proteins from this blueprint. tRNA molecules recognize specific sequences (three-letter codons) and deliver the corresponding amino acids needed to make a protein. Dr. Hsu recently found that certain starvation conditions can cause some tRNAs to be modulated in colorectal cancer cells. He will study the changes in tRNA levels that occur in response to cellular starvation states. He aims to shed light on how cancer cells adapt to starvation, which potentially can lead to new therapeutic approaches to target metabolic dependencies in cancer.

Dr. Hueschen studies the motility of Apicomplexan parasites, which cause malaria, foodborne illness (toxoplasmosis) and infections in immunocompromised cancer patients. These parasites move through the human body using a mechanism called "gliding" to migrate over host cells and through the surrounding extracellular matrix. Dr. Hueschen's goal is to understand how molecules inside the parasite are organized, coordinated and regulated to produce forces that direct movement. This research has the potential to aid in the development of therapies to prevent opportunistic infections.

Immune checkpoint inhibitors, a type of cancer treatment that helps immune cells identify and kill tumor cells, have been a major breakthrough in the treatment of many cancer types. Unfortunately, not all patients respond to this immunotherapy. Dr. Hughes [Robert Black Fellow] is studying how gut microbes improve response to immune checkpoint inhibitors. The bacterium Akkermansia muciniphila lives in the gastrointestinal tract and has been shown to improve response to immune checkpoint inhibitors via poorly understood mechanisms. Dr. Hughes aims to discover how A. muciniphila improves response to cancer immunotherapies and to design microbe-based therapeutic strategies that will further enhance cancer immunotherapy responses. Dr Hughes received her PhD from UT Southwestern Medical Center and her BS from Baylor University.