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Postbac Seminar Series: October 17, 2017

Series: Science Skills; Speaking

Oct 17, 2017

This event is recommended for: Postbacs.

Science isn't complete until the results have been shared with others, and talking about your results is one of the important ways of making them public. The Postbac Seminar Series provides a unique opportunity for two Postbacs each month to present their research to a diverse audience of their peers.  The atmosphere is relatively informal and non-threatening.  The series allows Postbacs who attend to learn about the different types of biomedical research being conducted at the NIH while meeting other postbacs.  Read more about the seminar series.

This month's presenters are:

David McKellar, NHGRI

Title: Identification of germline mutations contributing to leukemogenesis in Familial Platelet Disorder with associated myeloid malignancy

Summary: Allogeneic hematopoietic stem cell transplant is currently the only curative therapy for inherited bone marrow failure syndromes (IBMFS). However, in treating genetic disorders, matched sibling donors are not a viable option. Induced pluripotent stem cells (iPSCs) represent a promising solution for the development of autologous cellular therapies. Because iPSCs are patient-derived, deleterious germline mutations must be corrected before the reintroduction of cells to patients. Familial Platelet Disorder with associated myeloid malignancy (FPDMM) is a rare IBMFS characterized by dysmegakaryopoiesis, platelet dysfunction, and an increased risk of developing hematological malignancies. Because of the incomplete penetrance of malignancies in FPDMM, we sought to identify secondary germline mutations that may contribute to leukemogenesis. Here we report three potentially pathogenic mutations present in a pedigree of FPDMM. Using patient-derived iPSCs, we plan to test the functional effects of these mutations and better understand the roles they might play in the leukemogenic process.

Bio: David McKellar graduated from the Georgia Institute Of Technology in 2016 with a B.S. in Biomedical Engineering. Since joining NHGRI in June of 2016, he has worked on several projects under the guidance of Dr. Paul Liu in the Translational and Functional Genomics Branch.

 

Taylor Farley, NIAMS

Title: The TNF superfamily receptor, DR3, regulates innate immune responses in the gut

Summary: The mammalian intestinal tract is home to trillions of microbes that are key in priming both local and systemic immune responses. There are multiple mechanisms in place to allow for host-microbe interactions without promoting chronic inflammation, and breakdowns in these systems, such as polymorphisms at the locus, encoding the TNF superfamily cytokine TL1A, have been linked to intestinal bowel disease (IBD). We and others have recently found that TL1A can synergize with IL-23 to enhance the secretion of the barrier maintaining cytokine IL-22 by type 3 ILCs. To investigate the role of TL1A/DR3 interactions in gut homeostasis, we used the C. rodentium model of colitis in which IL-22 is required for disease resolution. Surprisingly, uninfected mice deficient in DR3 had similar levels of IL-22 as compared to their infected DR3 sufficient littermates, suggesting a breakdown in gut homeostasis and increased intestinal permeability. We are now exploring the mechanisms by which TL1A and DR3 modulate gut homeostasis in the absence of the adaptive immune system.

Bio: Taylor Farley graduated from Colorado State University in 2015 with a B.S. in Microbiology. She currently works in the laboratory of Dr. Richard Siegel of NIAMS where she studies the TNF superfamily cytokine TL1A and its receptor, DR3, in various autoimmune diseases.

 

 

Tom Hennigan, NCI

Title: Precise Enumeration of Cell Free DNA in Patient-Derived Cell Lines

Summary: I am currently working on developing a liquid biopsy, focusing on detecting circulating tumor DNA (ctDNA) from the blood of patients. By identifying unique molecular markers associated with cancer, with my focus being in prostate cancer, we can detect the disease early on with minimally invasive procedures, learning more about the molecular makeup of the genome, monitor patients throughout and after treatment.

In developing this assay, we focused firmly on detecting and identifying the minute amount of the ctDNA found in blood, which makes up around 0.1-0.01% of the cell-free DNA (cfDNA). By ligating on a seven-random base unique molecular identifier (UMI) on the molecules before any PCR-amplification, we are about to measure the amount of original ctDNA in the blood of patients. Throughout the heavy PCR-heavy protocol, we ligate on other sequences to run the samples on miSeq. Obtaining those sequences, we can use bioinformatics to filter out any duplicates and non-specific products produced during the PCR cycles.

By adopting such a molecular approach to diagnosis and monitor patients, we are continuing to advance the field of personalized medicine. Primers for the PCR can be adapted to patient-specific and provide a very sensitive way to detect cancer, even if any low levels.

Bio: Tom Hennigan was born in California but raised on the East coast in New Hampshire. He attended Endicott College in Beverly Mass where he obtained a B.S. in Biotechnology with his undergraduate thesis studying cancer proliferation and furthered this interest of the disease by pursuing a post-bacc at the NCI. He currently is researching how to develop a liquid biopsy to detect circulating tumor DNA and identify mutations unique to individual patients to monitor their disease during progression. His current academic passions are understanding the impact health disparities has on cancer rates in underserved communities and bringing innovative technologies to these vulnerable populations. Outside of academics and lab Tom enjoys cross-country biking, rock-climbing, and running mud runs.