mission & values

our mission

unravel the mysteries of the human genome in a collaborative, inclusive, and supportive research training environment

Each person’s distinct genetic, epigenetic, and environmental risk profile predisposes them to some phenotypes and confers resilience to others. My laboratory seeks to decode highly complex genetic insights into medically actionable information, better connecting the expanding list of genetic loci associated with human disease to pathophysiology. Our goal is to improve diagnostics, predict clinical trajectories, and identify pre-symptomatic points of therapeutic intervention.

Towards this, we employ a functional genomics approach that integrates stem cell models and genome engineering to resolve the impact of patient-specific variants across cell types, genetic backgrounds, and environmental conditions. Individually small risk effects combine to yield much larger impacts in aggregate, but the interactions between the myriad variants remain undetermined. Is there a “tipping point” between health and disease? Can ameliorative early interventions “untip” genetic disease risk? We seek to uncover disease-associated interactions within and between the cell types of the brain, querying the impacts of complex genetic risk within increasingly sophisticated neuronal circuits. Thus, we strive to translate risk “variants to genes”, “genes to pathways”, and “pathways to circuits”, revealing the convergent, additive, and synergistic relationships between risk factors within and between the cell types of the brain.

Even for highly penetrant mutations, a spectrum of phenotypes exist. We hope to understand the genetic, cellular, and environmental contexts that buffer genetic risk, and in doing so, develop interventions to help individuals achieve their greatest phenotypic potential. Thus, the variable penetrance of risk variants can be reframed as phenotypic resilience, evidence of biological “cures” capable of limiting, modifying, or preventing disease in individuals with otherwise high genetic predispositions. Such insights could identify therapeutics tailored to an individual’s specific risk profile, and so springboard the development of novel, personalized approaches to treat disease.

on diversity

We each absorb lessons of stereotypes, prejudice and discrimination.  Extensive data demonstrates that an implicit bias is shared by us all, independent of gender, race, ethnicity or sexual orientation (reviewed by [1]).  This is exacerbated by a relative reluctance among men, particularly scientists, to accept evidence of biases in science [2]. Coupled with the overwhelming preponderance of role models that are “pale, male and frail”, it is critical that as a field we work together to find new ways to foster and promote diversity in science. While data indicates that heterogeneous working groups produce higher quality science [3,4], neither gender nor racial equity has been achieved in the research community. As scientists trained to interpret complex datasets, we must enact data-driven initiatives: better identifying those policies that produce positive change and abandoning well-intentioned policies that exacerbate existing inequities. Senior scientists need to understand that the “best” student or faculty candidate need not be the one who most reminds them of themselves. Policies at the lab, department and institutional levels should be reexamined to be proactively anti- acist, striving to be mindful of the implications on financial sacrifice and work-life balance. Exceptional scientists frequently work outside our established scientific networks and pursue distinct research interests. Disadvantage is layered upon disadvantage. When I chaired a faculty search committee last year, the lack of diversity amongst the applicants was painfully apparent. Numerous think tanks have recommended actionable steps [5] to improve the recruitment, retention and accounting of diversity in science. Rather than strengthening the leadership skills of women and minorities (#leanin), institutions should endeavor to confront racism, which disadvantages equally qualified candidates by impacting our assessments of competence, hireability, and mentoring [6]. Effects must be measured not just in terms of diverse student and faculty recruitment and retention, but in perceptions of equity and justice as well. I commit to challenging my definition of “scientific excellence” at every level. 

Effort to recruit and support underrepresented students, without addressing fundamental inequities in our departments and institutions, also fails to address the needs of our underrepresented faculty peers. I commit to the following actions, and encourage other faculty to do the same: Advocate that future graduate and faculty searches include a “first look” for underrepresented scientists, broadly encouraging applicants without direct connections to our departments to apply and visit. Actively expand our professional network to include Black (and POC) scientists in our field, establishing new collaborations, properly citing papers, and nominating diverse scientists for seminars, conferences, and awards. For the journals at which we most frequently publish and review, discuss with the editors their efforts to increase diversity in editorial staff, reviewers and authors, and do likewise with the bodies to which we apply and review funding proposals. Equity and inclusion efforts alone are not enough: I pledge to better train, work with, and promote the work of underrepresented scientists.

References

1          Corrice, A. Unconscious Bias in Faculty and Leadership Recruitment: A Literature Review. AAMC 9 (2009).

2          Handley, I. M., Brown, E. R., Moss-Racusin, C. A. & Smith, J. L. Quality of evidence revealing subtle gender biases in science is in the eye of the beholder. Proc Natl Acad Sci U S A 112, 13201-13206, doi:10.1073/pnas.1510649112 (2015).

3          Campbell, L. G., Mehtani, S., Dozier, M. E. & Rinehart, J. Gender-heterogeneous working groups produce higher quality science. PLoS One 8, e79147, doi:10.1371/journal.pone.0079147 (2013).

4          Nielsen, M. W. et al. Opinion: Gender diversity leads to better science. Proc Natl Acad Sci U S A 114, 1740-1742, doi:10.1073/pnas.1700616114 (2017).

5          Smith, K. A. et al. Seven actionable strategies for advancing women in science, engineering, and medicine. Cell Stem Cell 16, 221-224, doi:10.1016/j.stem.2015.02.012 (2015).

6          Moss-Racusin, C. A., Dovidio, J. F., Brescoll, V. L., Graham, M. J. & Handelsman, J. Science faculty's subtle gender biases favor male students. Proc Natl Acad Sci U S A 109, 16474-16479, doi:10.1073/pnas.1211286109 (2012).