David W. Piston, Ph.D.

Edward Mallinckrodt, Jr. Professor and Head
Cell Biology and Physiology

Molecular Cell Biology Program
Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Biomedical Informatics and Data Science Program

  • 314-362-912

  • 4910 South Building

  • piston@wustl.edu

  • pistonlab.wustl.edu

  • Diabetes, Biophysics, Systems Biology, Computational Biology, Hyperspectral Imaging, Glucagon

  • Studies of the Molecular Pathways of Islet Hormone Secretion

Research Abstract:

The convergence of newly developed instrumentation and optical probes allows us to examine quantitatively dynamic processes within ever more complicated biological systems. These new tools are revolutionizing almost all fields of biomedical research, and we continue to optimize such methods and expand the scope of their applicability. In our lab, research questions are focused on a model multicellular system, the islet of Langerhans, which is the functional unit responsible for glucose-stimulated insulin secretion and glucose inhibition of glucagon secretion. The islet contains glucagon secreting Alpha-cells, insulin-secreting Beta-cells, and somatostatin-secreting Delta-cells, among others. The long-term goal of our work is to understand at a quantitative molecular level the subcellular, cellular, and multicellular mechanisms of islet function, and its role in the regulation of blood glucose under normal and pathological conditions. Rotation projects are available in all the lab’s research areas. The therapeutic success of insulin has led most islet research to focus on Beta-cells, although recent findings have strengthened our understanding of glucagon’s critical role in glucose homeostasis and the pathology of diabetes. Interactions with other islet cell types are thought to be involved in glucose-inhibition of glucagon secretion, since this inhibition is lost in vivo during Type 1 and advanced Type 2 diabetes, and in vitro when Beta-cells are isolated from the islet. While many compounds have been shown to inhibit glucagon secretion from islets, no consensus model has been reached. The secretory product of Delta-cells, somatostatin, is a promising molecular mediator of this interaction, but somatostatin alone does not inhibit glucagon secretion from isolated Alpha-cells. This suggests that other cell-cell interactions within the islet are required to combine with somatostatin for proper function. Using quantitative imaging methods and novel microfluidic devices, the dynamics of these molecular mechanisms can be followed in living cells within intact islets. These investigations utilize several available transgenic and tissue-specific knock-out mouse models with demonstrated phenotypes, as well as traditional biochemical and molecular biological approaches.

Mentorship and Commitment to Diversity Statement:
Biomedical
research can be very difficult and frustrating at times (if it was easy, we’d
just call it “search”).  Facing obstacle
after obstacle on the years-long path to completing a PhD can often become
all-consuming or discouraging, so maintaining balance is important.  While science is what we do, it is not who we
are, and mentoring in our lab aspires to cultivate and maintain relationships
that support and advance professional and personal development (https://pistonlab.wustl.edu/lab-values/).

I
have high expectations of every trainee in the lab, based in the belief that
all of our students are capable of excellence if they are willing to work hard
and learn to work smart.  The main goal
of my mentorship is to foster a growth mindset by helping students embrace
their experimental and conceptual struggles as learning opportunities that lead
to self-reliance, and in turn, boost their self-confidence.  One of my favorite parts of mentoring is
helping students realize that these struggles are common and a normal part of
developing expertise rather than a lack of ability.  While this mentoring can improve the outcome
for all students, I have found it to be even more important for students from
diverse groups including women, first-generation college students, and underrepresented
groups to thrive in graduate school. 

In the lab, my mentoring
style is hands-off, but I try to be visible in the lab and available to support
students as needed.  In addition to
weekly lab meetings, I schedule one-on-one meetings with students to discuss
both the big picture and details of their research project.  Students come to the research lab with drastically
different motivations and levels of preparation, so the frequency of these
meetings is based on the student’s needs, and has varied from weekly to every
few months.  As a lab, we also encourage
students to take advantage of their peers as mentors. 

Selected Publications:

Le Marchand, S.J., D.W. Piston. 2010. Metabolism and Calcium Dynamics in Glucose-Mediated Suppression of Glucagon Secretion from -Cells in Intact Pancreatic Islets. J. Biol. Chem. 285:14389-14398. PMCID: PMC2863245

Gunawardana, S.C., D.W. Piston. 2012. Reversal of Type 1 Diabetes by Brown Adipose Tissue Transplant. Diabetes. 61:674-682. PMCID: PMC3282804

Ustione, A., D.W. Piston. 2012. Dopaminergic Regulatory Feedback in Mouse Pancreatic β-Cells. Mol. Endocrin. 26:1928-1940. PMCID: PMC3487623

Benninger, R.K.P., T. Hutchens, W.S. Head, M. Zhang, S.J. Le Marchand, L.S. Satin, D.W. Piston. 2014. Intrinsic islet heterogeneity and coupling determine spatiotemporal calcium wave dynamics: verification of a mathematical model of the islet. Biophys. J. 107:2723-2733. PMCID: PMC425517

Hutchens, T., D.W. Piston. 2015. EphA4 Receptor Forward Signaling Inhibits Glucagon Secretion in α-cells. Diabetes. 64:3839-3851. PMCID: PMC4613968

Cranfill, P.J., M.A. Baird, J. Allen, Z. Lavagnino, H.M. de Gruiter, G.-J. Kremers, M.W. Davidson, A. Ustione, D.W. Piston. 2016. Quantitative Assessment of Fluorescent Proteins. Nat. Methods. 13:557-562. PMCID: PMC4927352

Lavagnino, Z., J. Dwight, A. Ustione, T.-U. Nguyen, T.S. Tkaczyk, D.W. Piston. 2016. Snapshot hyperspectral light-sheet imaging of signal transduction dynamics in intact live pancreatic islets. Biophys. J. 111:409-417. PMCID: PMC4968423

Reissaus, C.A., D.W. Piston. 2017. Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudo-Islets. Diabetes. 66:960-969. PMCID: PMC5360306

Foust, D.J., A.G. Godin, A. Ustione, P.W. Wiseman, D.W. Piston. 2019. Two-Color Spatial Cumulant Analysis Detects Heteromeric Interactions between Membrane Proteins. Biophys. J. 117:1764-1777. PMCID: PMC6838761

Hughes, J., J.H. Cho, H.E. Conway, M.R. DiGruccio, X.W. Ng, H.F. Roseman, D. Abreu, F. Urano, D.W. Piston. 2020. Primary cilia control glucose homeostasis via islet paracrine interactions. Proc. Nat. Acad. Sci. (USA). 117:8912-8923. PMCID: PMC7184063

Last Updated: 4/29/2021 9:44:43 AM

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