Postbac Spotlight—Translational Research, The Best of Both Worlds

Sarah Cook, postbac at the Laboratory of Immune System Biology, poses for a photo in the lab

Sarah Cook is a postbac in the Molecular Development of the Immune System Section of the Laboratory of Immune System Biology. Read Sarah’s postbac spotlight, where she details her postbac experience in the unique setting of the NIH Clinical Center and how this experience has influenced her decision to pursue a career in medicine and translational research.

Credit
NIAID

Sarah Cook is a postbac in the Molecular Development of the Immune System Section of the Laboratory of Immune System Biology. Read Sarah’s postbac spotlight, where she details her postbac experience in the unique setting of the NIH Clinical Center and how this experience has influenced her decision to pursue a career in medicine and translational research.

Credit: NIAID

Sarah Cook is a postbac in the Molecular Development of the Immune System Section, Laboratory of Immune System Biology. Sarah details her postbac experience in the unique setting of the NIH Clinical Center and how this experience has influenced her decision to pursue a career in medicine and translational research.

The NIH Clinical Center is a unique place to do research. It’s been especially helpful for me, as someone who was unsure about how to fuse my previous research interests with a growing interest in medicine, to learn about the translational research going on in NIAID. I’ve been working in the Molecular Development of the Immune System Section of the Laboratory of Immune System Biology, which studies patients with a spectrum of rare, inherited immunodeficiencies. These monogenic diseases are actually quite complex and difficult to diagnose because of overlapping clinical symptoms and incomplete trait penetrance. We use whole exome sequencing on patient samples to discover potential causal genetic variants that we can validate functionally with model systems.

Studying the cellular and biochemical effects of variants can offer new insights into mechanisms of the immune system. For example, I’ve been working closely with Dr. William Comrie, my postdoc mentor, to characterize an actin-related disease that was discovered in only five patients. These patients have biallelic loss-of-function mutations in the gene NCKAP1L, which encodes a protein called Hem1 and is expressed specifically in the immune system. We were able to distinguish abnormal cellular functions related to defective actin polymerization—like impaired neutrophil chemotaxis and T-cell immune synapse formation—from those that weren’t expected based on known functions of the protein. In this way, we discovered a novel connection between Hem1 and the mTORC2 regulatory system.

It’s been exciting and challenging to incorporate a molecular understanding of immunology with clinical data from patients. This experience has definitely guided my decision to apply to research-oriented medical schools.

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