| College: | Yale University |
| Degree: | BS, Applied Mathematics & Chemistry |
| Mentor(s) |
John Stamatoyannopoulos |
| Primary Department | Genome Sciences |
| Dissertation Title: | Transcriptional Specificity of Chromatin Remodelers |
| Defense Date: | 2019-05-30 |
| Title: | Resident |
| Location: | University of California-San Francisco ,
San Francisco, CA |
Chris Arakawa's dissertation work in the Department of Bioengineering reflects a continuing translational research trajectory focusing on biomaterials and regenerative medicine that began when he was an undergraduate at UCLA. For his PhD at the UW, Chris engineered new photochemically controllable biomaterials that he used in conjunction with induced pluripotent stem cells and organoids to model renal and cardiovascular biology. His research was highly collaborative and interdisciplinary. He was co-mentored by two faculty (Drs. Cole DeForest and Ying Zheng) and worked across five different labs, including one in Japan, where Chris spent half a year. In one particularly multidisciplinary and innovative application, he studied how falciparum malaria distributes through 3D models of blood vessels.
Jacob Baudin completed his dissertation research under the mentorship of HHMI Investigator, Dr. Fred Rieke, in the Department of Physiology and Biophysics. Jacob studied the neuroscience of color vision. Employing a multidisciplinary experimental and computational approach, Jacob discovered unexpected heterogeneity among distinct cone cell types in the primate retina, extending throughout all levels of spatial, spectral, and neurocortical organization. Jacob has additionally distinguished himself due to an enduring interest in computational science. Concurrent with, yet independently from, his PhD research, Jacob worked with Dr. Shwetak Patel, a Professor in the UW School of Computer Science & Engineering, to apply machine learning to develop a smartphone app to measure pupillary light responses, for traumatic brain injury diagnosis. This passion led him to perform a summer internship culminating in a one-year position as a software engineer at Google headquarters in Mountain View, California, in-between the conclusion of his dissertation research and before re-entering clerkships. At Google, Jacob developed medical diagnostic machine learning algorithms. While performing clerkships, Jacob has collaborated with MSTP alumnus and surgical resident, Dr. Katie Liu, to create a smartphone game controlled by skin electrodes recording muscle activity, in order to speed recovery from nerve injuries. The UW MSTP has a long history of MSTP students performing computational internships. In fact, UW MSTP alum, Bud Tribble, led development of the Apple Macintosh operating system while a student in our program; Dr. Tribble is a legendary senior executive at Apple and continues to develop health enabling technologies, such as the EKG features of the Apple Watch.
Elise Cai performed her dissertation research in the Molecular and Cellular Biology Program under the mentorship of Dr. Slobodan Beronja at the Fred Hutchinson Cancer Research Center. Elise addressed the clinically and scientifically important question of why the skin lesions in individuals with neurofibromatosis and other inherited disorders of RAS signaling tolerate a surprisingly high burden of oncogenic mutations and thereby resist malignant transformation. She discovered a new protein translational mechanism regulating production of a key ubiquitin ligase, involved in protein degradation. In collaboration with Dr. Andrew Hsieh’s lab at the Hutch, she discovered similar translational regulatory pathways involved in prostate cancer. During clerkships, Elise has helped organize a project delivering home health care during the COVID-19 outbreak.
David Caldwell performed his dissertation research in neurosciences through the Department of Bioengineering under the mentorship of Jeffrey Ojemann, M.D. in the Department of Neurological Surgery and Rajesh Rao, Ph.D. in the School of Computer Science and Engineering. David engineered new approaches for targeted direct electrical stimulation of the brain. His work was interdisciplinary and involved working with patients undergoing brain surgery, in vitro systems, computational modeling, and electrical device circuit design. David’s research was highly collaborative and involved a summer spent performing research at the University of Freiburg, in Germany. The neuroprosthetic devices he developed are leading the way to help treat stroke and other brain injuries. David has continued research while performing clerkships. In one project addressing craniectomy methods, David developed software to perform quantitative image analysis on CT scans. In another project, David addressed disparities in clinical trials research and developed software to analyze a large clinical trials database.
Ken Chen performed his dissertation research in the Department of Genome Sciences under the mentorship of Dr. Matt Kaeberlein, one of the world’s leading authorities on the biology of aging. Ken’s project was multidisciplinary, encompassing both bioengineering and genetics. He studied yeast, an established model organism for investigating aging, and engineered a microfluidic device to capture aged yeast cells. He discovered that as yeast age, they become deficient in iron prosthetic groups needed for aerobic metabolism and DNA replication fidelity. His were the first studies to implicate iron metabolism in aging. Interestingly, since then, human genome-wide association studies have similarly identified iron metabolism as a significant genetic pathway contributing to human aging.
Miles Freeman is a student in the Morehouse School of Medicine/University of Washington MSTP pathway. He earned his PhD in the Molecular and Cellular Biology interdisciplinary program in the laboratory of Dr. Robb MacLellan in the Division of Cardiology in the Department of Medicine at the University of Washington. The goal of Dr. Freeman’s research is to promote cardiac regeneration in patients after suffering a myocardial infarction. He has pursued a new strategy of coaxing otherwise terminally differentiated cardiac myocytes to re-enter the cell cycle. An epigenetic mechanism limiting cardiac myocyte cycling in adult cardiac myocytes involves trimethylation of lysine-9 of Histone H3 (H3K9me3), a modification associated with repressed chromatin, which silences expression of cell cycle genes and ordinarily restricts heart regeneration following injury. He found that KDM4D, a demethylase targeting H3K9me3, can reactivate cell cycle gene expression and mitigate cardiac myocyte damage in response to ischemic injury. He is currently completing the clinical phase of medical school at Morehouse School of Medicine in Atlanta.
Madeleine Geisheker received her Ph.D. in Genome Sciences under the mentorship of HHMI Investigator Dr. Evan Eichler. Her dissertation research involved the discovery of de novo pathogenic mutations in nearly 20,000 individuals with intellectual disability, resulting in the identification of new cellular pathways responsible for autism and other developmental disorders. Madeleine’s approach was multidisciplinary, employing a combination of experimental and computational methods, and highly collaborative, involving other departmental labs as well as investigators from around the world. Her findings pave the way for new clinical diagnostic testing and treatment approaches for autism.
Rini Kasinathan completed her dissertation research in the Molecular and Cellular Biology program at the Fred Hutchinson Cancer Research Center under the mentorship of HHMI Investigator, Dr. Harmit Malik. Rini’s research focused on the evolutionary relationship between transcription factors and the chromatin with which they engage in order to effect gene regulation. Her approach was multidisciplinary, employing in vitro studies in conjunction with Drosophila models, computation, and next-generation DNA sequencing. While in clerkships, Rini has initiated clinical translational research addressing how COVID-19 is impacting participants in opioid recovery programs. Rini and her older brother, Siva, now a resident in the physician-scientist Pediatric Residency track at Stanford, share the distinction of being the only two siblings in the history of our program.
John Lazar performed his dissertation research in the Department of Genome Sciences under the mentorship of Dr. John Stamatoyannopoulos. John employed experimental and computational approaches to investigate how mutations and dysregulation of chromatin remodelers contribute to cancer. Dr. Stamatoyannopoulos is a leader of the ENCODE consortium, a worldwide collaboration that aims to identify functional elements in the human genome. John played a pivotal role in the Stamatoyannopoulos laboratory’s participation in ENCODE. John was instrumental in developing a cutting-edge new course for MSTP and other medical students at the University of Washington, focused on sequencing the genome of a cadaver undergoing dissection in the medical school human anatomy course. This was the first course of its kind for any medical school. For five years, John participated in the design, teaching, genome sequencing, and data analysis. Two papers were collaboratively written through the aegis of this course.
Juhye Lee earned her PhD in Genome Sciences. She performed her research under the mentorship of Dr. Jesse Bloom at the Fred Hutchinson Cancer Research Center. Juhye studied the evolutionary dynamics of the influenza virus. Specifically, using high-throughput approaches to uncover which mutations allow the virus to escape from antibodies. She ultimately hopes this work will enable forecasting of influenza evolution.
Nicole Naiman's dissertation research in Molecular and Cellular Biology follows a sustained research trajectory focusing on HIV that began as an undergraduate at The Ohio State University and as a postbaccalaureate fellow at the NIH. Under the mentorship of Dr. Julie Overbaugh at the Fred Hutchinson Cancer Research Center, Nicole’s Ph.D. research focused on mother-to-child HIV transmission. Nicole mapped HIV epitopes recognized by maternal antibodies and defined those that were protective and, unexpectedly, identified epitopes that when targeted by antibodies are actually associated with worse outcomes and that should therefore be avoided when considering vaccine and therapeutic strategies.
Mark Ragheb's dissertation work in Molecular and Cellular Biology at the University of Washington MSTP reflects a continuing passion for research on tuberculosis that began while he was an undergraduate at Harvard. For his Ph.D. research, performed under the supervision of Dr. Houra Merrikh in the Department of Microbiology, Mark developed a highly innovative strategy for blocking antibiotic resistance in tuberculosis by identifying factors contributing to bacterial diversity and inhibiting evolution, itself. His work was multidisciplinary, employing both experimental and computational approaches and highly collaborative, involving contributions from within and outside the institution. His studies commanded attention from the scientific and lay press, such as in The Atlantic (https://www.theatlantic.com/science/archive/2018/11/anti-evolution-drug-vs-antibiotic-resistant-superbugs/575929/).
Rebecca Resnick received her Ph.D. through the Molecular and Cellular Biology program at the Fred Hutchinson Cancer Research Center under the mentorship of Stephen Tapscott, M.D., Ph.D. (who is also an Associate Director of our MSTP). Her dissertation research was focused on the molecular genetic pathogenesis of facioscapulohumeral muscular dystrophy (FSHD). The genetics of FSHD are extremely complicated and involve subtelomeric repeats, a permissive genotype at a different locus, and activation of pseudogenes. Nevertheless, Rebecca took the bull by the horns and explored how the FSHD-associated gene DUX4 facilitates genomic incorporation of a recently discovered new class of histone variants. While in clerkships, Rebecca engaged in a new translational research project studying COVID-19 in pregnancy.
Jesse Resnick performed his dissertation research in the Neuroscience program under the expert mentorship of UW MSTP alumnus, Jay Rubenstein, M.D., Ph.D., in the Department of Otolaryngology. Jesse’s research focused on improving cochlear implants for deafness. Despite the success of cochlear implants, there is much that remains unknown about how they activate auditory nerves. Jesse’s dissertation sought to address this knowledge gap using a multidisciplinary and collaborative approach employing biophysical simulations, human psychophysics, animal models, and electrical engineering. In line with Jesse’s interests in otolaryngology, while in clerkships, he has initiated clinical translational research addressing the utility of sentinel node biopsy in patients with malignant melanoma involving the head and neck.
Alex Salter performed his dissertation research through the Molecular and Cellular Biology program at the Fred Hutchinson Cancer Research Center, under the mentorship of Dr. Stanley Riddell, who is among the founders of cellular immunotherapy. Alex employed a multidisciplinary approach to improve chimeric antigen receptor (CAR) T-cell cancer therapies, utilizing mass spectrometry, preclinical immunodeficient mouse models, and human clinical trial data, to, among other things, engineer highly innovative logic-gated CAR T-cells. Alex has been highly recognized for his research. He was named to Forbes Magazine’s “30 Under 30” list in 2019 and has met with former United States Vice President Joe Biden to advise on the Cancer Moonshot initiative.
Shivam Zaver’s dissertation research in the laboratory of Dr. Joshua Woodward in the Department of Microbiology addresses innate immunity. DNA is ordinarily located in the nucleus of a cell. DNA can be found outside of the nucleus, however, during a bacterial or viral infection. Once detected where it does not belong, DNA stimulates an interferon-mediated immune response, mediated by a cyclic dinucleotide, which functions as a second messenger. How the cyclic dinucleotide crosses the cell membrane had been unknown. Shivam found that the second messenger is taken up by the cell through a folate transporter. Consequently, inflammation can be inhibited by folate. His discovery explains how some anti-inflammatory medications, such as sulfasalazine and methotrexate, achieve their effect and has implications for developing new forms of immunotherapy for cancer and infectious disease.
Qian Zhang completed her dissertation research in the Department of Biostatistics, under the mentorship of distinguished biostatistical geneticist, Dr. Bruce Weir. Qian pioneered new quantitative methods for measuring ancestry-specific allele frequencies that are helping to improve the accuracy of genetic testing, including genome wide association analyses. Computational methods she has developed have led to better understanding of the genetic architecture of hyperlipidemia. During clerkships, Qian has undertaken radiology and radiation oncology research projects, involving extraction and quantification of imaging data.
John Lazar performed his dissertation research in the Department of Genome Sciences under the mentorship of Dr. John Stamatoyannopoulos. John employed experimental and computational approaches to investigate how mutations and dysregulation of chromatin remodelers contribute to cancer. Dr. Stamatoyannopoulos is a leader of the ENCODE consortium, a worldwide collaboration that aims to identify functional elements in the human genome. John played a pivotal role in the Stamatoyannopoulos laboratory’s participation in ENCODE. John was instrumental in developing a cutting-edge new course for MSTP and other medical students at the University of Washington, focused on sequencing the genome of a cadaver undergoing dissection in the medical school human anatomy course. This was the first course of its kind for any medical school. For five years, John participated in the design, teaching, genome sequencing, and data analysis. Two papers were collaboratively written through the aegis of this course.
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