Sheila S. Iyer – Danaher Corporation Scholar
Undergraduate Scholar, Biomedical Engineering
Johns Hopkins University

Describe how an ARCS Award will benefit your Research:
Curiosity about how things work has always propelled my life. In middle school, I looked through a microscope at a cell and saw the nucleus, mitochondria, and other organelles, each with distinct functions. Staring into the 6-micrometer nucleus, I was amazed at how differential expression of DNA creates different types of cells - muscles, skin, entire systems! I became fascinated by genomics, the study of DNA, and how it shapes us. It amazed me how a seemingly random string of letters was the code for our life, and I was struck by the innovative ways scientists were extracting meaning from DNA. I was fortunate to attend Thomas Jefferson High School for Science and Technology (TJHSST), a STEM-intensive magnet high school that was ranked #1 in the country and requires a rigorous application process. I took advanced courses in DNA science, artificial intelligence, computer vision, and neurobiology and performed research on nerve regeneration in crayfish in our neuroscience research laboratory. This incubated my love and interest in researching the intersection of medicine and computer science for a data-informed approach to studying disease mechanisms.

Attending a Sigma Xi conference in my junior year of high school, I watched Dr. Ben Langmead of Johns Hopkins University present a talk on making the most of petabytes of genomic data. This began my foray into computational genomics when I interned for him and worked on a project studying the reference bias of DNA sequence alignment tools; I continued my work as an undergraduate at Johns Hopkins University (JHU), working on creating Biastools, a reference bias diagnostics pipeline deployed as a command line tool. At JHU, I was awarded a research grant by the Office of Undergraduate Research and worked in Dr. Steven Salzberg’s lab, devising a pipeline for assembling and identifying nuclear mitochondrial insertions that can cause diseases, including cancer, if inserted into oncogenes.

With my growing interest in medicine and the clinical implications of genetic variation, I wanted to study how specific genetic variants affect disease pathogenesis and how biomarkers can be used clinically. I secured a research position in the Armanios lab at the JHU School of Medicine, where I have created analysis pipelines to study large biobanks of sequencing data along with clinical phenotypes to study clonal hematopoiesis (CH, a precursor to cancer) as an adaptive evolutionary response to telomere dynamics. I discovered a novel CH mutation that is more prevalent among individuals with short telomeres. I also used my analysis pipeline to identify long telomere candidate genes, which can be important cancer risk factors. We use an innovative approach focused on applying computational techniques to analyze a broad population of individuals to identify candidate genes or specific mutations involved in disease pathogenesis.

This is followed by wet-lab functional assays to determine mechanisms behind disease development and to understand the potential for diagnostic utility for patients. Through my research experiences, I have found that research is a beautiful expression of creative thinking that allows us to unpack how the world works. Researchers are like magicians coming up with new tricks; they must think about their goals, analyze existing information, and devise novel, out-of-the-box methods to drive discovery. With the support of the ARCS award, I aim to continue studying mechanisms behind TERTp clonal expansion and the role of genomic variants in disease pathogenesis. In the Armanios Lab, I was named a Turock Scholar and received a research grant through JHU’s Bloomberg Distinguished Professor program for prior research. I know how research grants support creative problem-solving. This award money will also reduce my undergraduate tuition. What I am most excited about is also the opportunity to be exposed to the rich network within ARCS, including former JHU scholars and other alumni. This will enable me to hear and learn from the experiences of others who are at different stages of their research careers.