Current Work


I am working in Hunter Fraser’s lab on several projects investigating the role of changes in gene expression on complex human phenotypes, including susceptibility to a range of inflammatory diseases and major depressive disorder.

Influence of Chromatin State on Disease Pathology

While many diseases have been studied extensively by genome wide association studies (GWAS), very few of these studies have been able to shed much light on the molecular changes that give rise to disease pathology. Using a new chromatin dataset that we have created, we are able to identify the individual chromatin state at hundreds of thousands of SNPs in the genome across a thousand individuals in ten human populations. Using this data, along with a risk allele database I created (the largest of its kind), I have been investigating how the chromatin state of different risk alleles can lead to variations in disease pathology and other phenotypes. This work can help us to understand the mechanisms by which genome variation can give rise to human disease. This research is currently in preparation for publication.

Major Depressive Disorder

Very little is known about the pathophysiology of major depressive disorder (MDD), or how it is inherited, despite increasing evidence that it is more than just a psychological phenomenon. I have been re-analyzing RNA-sequencing data from the work by Battle et al.[1] to ascertain if major depressive disorder can be partially explained by variation in the abundance of alternate splice-forms of genes, particularly those in relevant biochemical pathways, or by changes in allele-specific gene expression. This project is nearing conclusion pending the completion of my work on chromatin state and disease risk.

Evolution of Mitochondrial Abundance

I worked on a method to infer mitochondrial DNA abundance directly from a meta-analysis of GWAS data from 125,000 individuals in an effort to use this information to shed light on the mechanisms controlling mitochondrial abundance. These mechanisms are not well understood, and low or high relative levels of mitochondria have been implicated in many diseases.

Future Interests


It is my hope to combine academic research with clinical practice in the future. Several different research avenues currently interest me, all arranged around methods of helping the underserved and understanding disease, and which path I take will depend on the lab/group I end up working with in medical school. Below are my current interests.

The Evolution of Pathogenicity

I am very interested in how human diseases, particularly infectious diseases, evolve and adapt around our efforts to treat them. My interest in this area encompasses how pathogens circumvent immune surveillance and how they evolve resistance to the drugs we have discovered to treat them. Perhaps the largest looming crisis for human health is the rapid evolution of antibiotic resistance(a)The natural propensity for this evolution is brilliantly displayed in this video from Michael Baym (then in the Kishony lab[2]. The exact burden of antibiotic resistance is extremely difficult to estimate [3] but we do know that resistance across the board is evolving very rapidly [4] and that bacterial infectious are responsible . Given the declining rate of discovery of new antibiotic classes by traditional drug screening, and the increasing use of antibiotics globally (70 billion doses per year in 2010, up from 53 billion in 2000 [5,6] (b)”antibiotic usage in 2010 was dominated by penicillins, cephalosporins, macrolides, fluoroquinolones, trimethoprim and tetracyclines” from Woolhouse, 2016 [3,6]), it is clear that more research on how drug resistance evolved, and on strategies to interfere with that evolution, is required.

Cultural, Social, and Economic Barriers to Health Care

From my own experience volunteering at Santa Clara Valley Medical Center’s Emergency Department, I have seen how economic barriers to health care can be devastating, even within a wealthy community such as Northern California. When combined with cultural barriers, such as language barriers or differing beliefs on the ‘right’ way to treat disease, and social barriers, such as feeling disrespected by medical providers, the intersectionality of disadvantage can result in disastrous outcomes. In my short time volunteering in a single county emergency department I witnessed several needless deaths and countless cases of people living with illnesses that could be effectively treated. This should not happen in a modern health system, and I was left feeling that we have to do more to ensure better health outcomes for everyone in our society. Our medical system responds well (albeit slowly) to hard data, and I believe that there is plenty of room for public health research on the local determinants of disease and the best way to ensure better outcomes for all those who use our medical system.

Emerging Infectious Diseases

In the last few years, we have witnessed the emergence of Zika virus and the re-emergence of Ebola virus alongside the emergence of other less publicized and more easily controlled zoonotic infections. As human populations continue to encroach on wild areas, it is likely that more such diseases will appear. I am interested in the evolution of specific traits that allow diseases to ‘jump’ species barriers and enter new populations, as well as in the immune mechanisms we use to fight them.

Medicine in Austere Environments

I am very interested in the practice of medicine in austere environments, both globally and in the United States, particularly in areas of poverty and natural/man-made disaster, but also in inhospitable natural wild environments. In such places, resources are limited and prioritization of resources is essential. The practice of medicine in such places has historically suffered from a dearth of supporting research and has relied instead on the experience and best guesses of dedicated clinicians. While such experience should not be discounted, the ability of well-executed research to improve care should also not be discounted. As I progress through my medical education, I wish to investigate ways to improve access to access to high-quality healthcare in places where such access is intrinsically limited.

Bibliography


1.
Battle A, Mostafavi S, Zhu X, Potash J, Weissman M, McCormick C, et al. Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res. 2014;24: 14–24. [PubMed]
2.
Baym M, Lieberman T, Kelsic E, Chait R, Gross R, Yelin I, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353: 1147–51. [PubMed]
3.
Woolhouse M, Waugh C, Perry M, Nair H. Global disease burden due to antibiotic resistance – state of the evidence. J Glob Health. 2016;6: 010306. [PMC]
4.
Ventola C. The Antibiotic Resistance Crisis: Part 1: Causes and Threats. P T. 2015;40: 277–283. [PMC]
5.
Antimicrobial Resistance: Global Report on Surveillance [Internet]. World Health Organization. World Health Organization; 2014 pp. 1–40. Available: http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf?ua=1 [Source]
6.
Van B, Gandra S, Ashok A, Caudron Q, Grenfell B, Levin S, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14: 742–50. [PubMed]

Footnotes   [ + ]

a. The natural propensity for this evolution is brilliantly displayed in this video from Michael Baym (then in the Kishony lab[2]
b. ”antibiotic usage in 2010 was dominated by penicillins, cephalosporins, macrolides, fluoroquinolones, trimethoprim and tetracyclines” from Woolhouse, 2016 [3,6]