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Dr. Gihana [The Mark Foundation for Cancer Research Fellow] investigates the role of cellular morphology in mediating the oncogenic signaling of the gene RAS in pancreatic cancer. RAS is altered in more than 30% of human cancers, making it one of the genes most affected by cancer-causing alterations. Oncogenic RAS induces pronounced changes in cell morphology. Dr. Gihana aims to understand how the changes in cell morphology contribute to the potential of RAS to cause cancer.
Dr. Lin [Walter Isaacson Fellow] is studying how hepatitis C virus (HCV) rewires cell biology and causes liver cancer. Modern HCV antiviral therapies are effective in curing hepatitis, but puzzlingly, recovered patients sometimes still develop cancer. This suggests that infection and subsequent inflammation permanently alter liver cells, but how this leads to cancer remains unclear. Dr. Lin is developing a CRISPR-based molecular "recorder" to determine whether cells that become more cancer-like have a history of infection and inflammation.
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.
Dr. Kim [HHMI Fellow] is studying the molecular links between cancer cells undergoing metastasis and formation of the face during development (known as craniofacial development). Both craniofacial and cancer cells must enter a migratory state triggered by certain key transcription factors including TWIST1. However, the exact role of TWIST1 appears to vary across cell types, which might explain some of the differences between cells found in various cancers and in normal craniofacial development. Dr.
Dr. Niekamp [Dennis and Marsha Dammerman Fellow] studies how gene expression programs are regulated in normal and cancer cells. The ability to switch specific genes "on" and "off" is partly encoded by multiprotein complexes competing for access to target DNA sequences in chromatin structures. The relative distribution of these activating or repressive complexes along chromatin regulates gene expression, and a shift in the balance of these complexes is a hallmark of many cancers. Dr.
Dr. Eisen [David Ryland Fellow] studies how a class of enzymes known as the Tec kinases help to activate the immune response. Two of these kinases, Itk and Btk, are remarkably similar in sequence composition and structure but play distinct roles in immune cells. Dr. Eisen is using high-throughput methods to understand the differences between these enzymes. This work will also aid in the overall molecular understanding of Btk, which is a therapeutic target of B-cell lymphoma and is inhibited by the chemotherapeutic ibrutinib.
Dr. Zhang [Merck Fellow] aims to address what information is sensed and relayed by sensory nerve fibers within the pancreas. Internal organs receive sensory nerve fibers that constantly monitor their conditions but the exact mechanism for this type of sensation is understudied. As an organ that is instrumental to blood glucose regulation and food digestion, the pancreas receives a host of different sensory nerve fibers, but the information conveyed by these fibers and their function are still yet to be precisely defined.
Dr. Sullivan [Merck Fellow] studies the processes that lead to opportunistic infections affecting cancer patients. The human body, which is a hostile environment for pathogens, is well-equipped to fend off infections from most bacteria. However, cancer and chemotherapy can cause inflammation, tissue damage, and impairment of the immune system in ways that leave patients vulnerable to bacterial infection. These opportunistic infections are challenging to treat, as antibiotics often have little effect on these bacteria. Dr.
Dr. Sima [HHMI Fellow] is investigating the relationship between sleep disturbances and cancer development. She is dissecting how neurons controlling the sleep-wake cycle affect immune functions that impact cancer. Dr. Sima will also examine the complementary problem of how tumor growth and chemotherapy contribute to sleep issues by analyzing gene expression patterns in neurons that regulate the sleep-wake cycle.
Dr. Puchades studies ion channels – proteins embedded in the membrane surrounding a cell. They act as molecular gates, opening in response to diverse stimuli to allow ions to flow into cells. The essential ion channel TMEM16A is required for many fundamental physiological processes, including neuronal signaling, muscle contraction, and salivary gland secretion. In cancer cells, increased activity of TMEM16A is closely linked to metastatic progression in esophageal, gastric, and pancreatic cancers. Dr.