David C. Samuels’ biography

 

EDUCATION

1983, BA               Washington University in St. Louis (Physics)

1990, PhD            University of Oregon (Physics)

POSTDOCTORAL TRAINING

1990-1992            Postdoctoral Fellow, Center for Turbulence Research
Stanford University and NASA Ames Research Center

1993-1996            Postdoctoral Research Assistant, Department of Physics
Emory University

Faculty Positions

Academic Appointments

1996-2001            Lecturer
School of Mathematics
University of Newcastle, UK

2001-2002            Reader in Applied Mathematics
Department of Mathematics
University of Newcastle, UK

2002-2009            Assistant Professor
Virginia Bioinformatics Institute
Virginia Tech, USA

2009-Present     Associate Professor
Department of Molecular Physiology and Biophysics
Center for Human Genetics Research
Vanderbilt University School of Medicine

Vanderbilt University

“I don’t think anyone should write his autobiography until after he is dead” – Samuel Goldwyn

 

Graduate school (1983-1990)

My PhD work was in simulation of quantized vortex filaments in Helium II, in Russ Donnelly’s lab at the University of Oregon.  While that seems a million miles away from what I do now, there is a common thread. Back then, I was the sole theoretical physics student embedded in a low-temperature experimental lab.  I was at a keyboard while everyone else had a wrench or a soldering iron in their hands. That experience set the pattern that I continue in my collaborations today with wet-lab faculty and clinicians.

My thesis was analysis of the stability of simple plane waves on vortex filaments.  I found that on long time scales plane waves were unstable and the energy of the plane wave would slowly concentrate into a localized soliton pulse. Eventually, the energy now in the soliton pulse would redistribute and reform the initial plane wave exactly.  This long term oscillation between the plane wave and the soliton would continue indefinitely.  The oscillation was periodic for small amplitude waves, but became chaotic for larger amplitude waves.  This is an example of Fermi-Pasta-Ulam dynamics.

 

First postdoc, Stanford and NASA Ames (1990-1992)

I was fortunate to be chosen for a dream postdoc at the Center for Turbulence Research, split between the Stanford campus and the NASA Ames Research Center at Moffet Field.  There I had freedom to do basically anything I wanted, and excellent supercomputer facilities.  I used this time to apply my PhD work to the problem of superfluid turbulence, specifically the problem of interacting normal fluid and superfluid vorticity.

 

Second postdoc, Emory (1993-1996)

After a short break, I decided to try a new research direction (since there were no research funds for superfluid turbulence at that time).  I took a post-doc working with George Hentschel in the Emory University physics department, on simulations of neuron growth.   Together with Alan Fine, we developed a simulation model of the growth of the cytoskeleton of a cell, forming protuberances in the cell membrane that developed into one (or sometimes two) long axon and several slower growing dendrites.

 

Faculty position, University of Newcastle-upon-Tyne, UK (1996-2002)

My first faculty position was in the School of Mathematics at the University of Newcastle.  Here, I returned to superfluid turbulence research, through a long and fruitful collaboration with Carlo Barenghi.  As I settled in to faculty life and teaching intro calculus, I began to get calls from the Medical School faculty saying that they were glad the School of Maths had finally hired a mathematical biologist (based on my neuron simulations) and could I come over to talk over some ideas.  Most of these calls went nowhere; however one visit was by a young neurologist / PhD student, Patrick Chinnery, with a very interesting and plausible idea for a simulation. That led to our first collaboration on a simulation of the replication of the thousands of copies of the mitochondrial DNA (mtDNA) molecule in a single cell.

At that time there was the idea that the amount of mutated mtDNA molecules in a patient’s cells could increase over time due to a “replicative advantage” to the mutant mtDNA molecule over the wild-type mtDNA.  While this replicative advantage might be possible for the common deletion due to its small size (and thus faster replication), it was not reasonable for the many point mutations that also cause mitochondrial disease.  Patrick and I designed a model of mtDNA replication where both mutant and wild-type mtDNA had equal replication chances (a Neutral Drift model).  The necessary feature of this model was a feedback mechanism where the overall replication rate (over both mutant and wild-type mtDNA) was increased if the number of wild-type mtDNA fell below a target number.  This represented a response of the cell to insufficient mitochondrial function (using wild-type mtDNA and a proxy for proper mitochondrial function). We called this the maintenance of wild-type model.

That work, and the experimental work of many other labs, shifted the standard paradigm away from replication advantage and towards the neutral drift model.  However, pendulums do tend to swing back again.  Some of our recent work indicates that certain somatic mtDNA mutations do indeed have a replication advantage.  The surprise is that the replication advantage is tissue dependent, with specific mutations increasing with age only in specific tissues.  Life is more complex that we can imagine.

 

Faculty position, Virginia Tech (2002-2009)

For family reasons, I chose to return to the US after six interesting years in the UK.  In order to concentrate on the mitochondrial research, I took a position at the newly formed Virginia Bioinformatics Institute at Virginia Tech (now known as the Biocomplexity Institute).  Here my research interest in mtDNA replication developed into a new program on the possible mechanisms of toxicity of nucleoside analogs used to treat HIV infection.

 

Faculty position, Vanderbilt (2009-present)

At Virginia Tech I found that I missed the direct interaction with the clinicians in a Medical School that I had enjoyed at Newcastle.  To remedy this, I moved my research group to Vanderbilt University, with a faculty position in the Vanderbilt Genetics Institute and the Department of Molecular Physiology and Biophysics. So in a way I am back in physics once again. At Vanderbilt I have very active collaborations with the large HIV research community here, as well as new directions in cardiology, critical care, and ophthalmology.  I served as the Director of Graduate studies for the PhD program in Human Genetics from 2012-2019, and currently serve as the Director of that program.

A major draw to Vanderbilt for “dry-lab” researchers like me is the BioVU project.  BioVU is a biobank project, combining a de-identified version of the EMR together with stored DNA samples.  This allows us to carry out research projects on clinical data quickly and cheaply, without the complications of patient ascertainment and enrollment.  I serve as chair of the committee that reviews and approves research projects in BioVU, which has been the most effective way of learning study design that could be imagined.