Training Grant Recipients


 

TSRI Current Trainees (2016-2019)

 
 

Andrew Jewett, Ph.D. (08/20/19 - Present)          

Mentors: David Goodsell, Ph.D. and Stefano Forli, Ph.D.

Computational Modeling of Active Processes in HIV Assembly and Maturation

I have developed a method to build and efficiently simulate arbitrarily complex theoretical models of molecular machines in 3D (at the coarse-grained level). The method is called "Molecular Cellular Automata" (MCA). I will use it to simulate several theories of the HIV life cycle and compare the results with available experimental evidence. I will explore the spatial relationships and timing of the capture of RNA by gag at the cell membrane and the lateral assembly of gag into the lattice that drives budding. I will also explore reverse transcription within the viral capsid, exploring several conflicting hypotheses about the nature of RTC (reverse transcription complex) and its transition to the PIC (pre-integration complex). I will test several hypotheses regarding the oligomeric state and steric interactions of protease, reverse trsanscriptase, and integrase within gag-pol during the process of viral maturation. This kind of computational modeling is still in its infancy. New software tools may need to be developed. In addition to exploring these questions, one of my major goals is to create software that will enable other scientists to explore their own new questions, not only about viruses but about any process which may occur inside the cell. I will make sure my MCA tools are general, easy to use, and available to the public.

 

Raymond Pauszek, Ph.D. (08/01/19 - Present)           Mentor: David Millar, Ph.D.

Single-Molecule Studies of HIV-1 Gag Assembly

In this project, I will use single-molecule fluorescence microscopy to investigate the process of HIV-1 Gag assembly on viral genomic RNA one molecule at a time. Using this experimental system, individual fluorophore-labeled Gag molecules will be monitored and counted as they assemble around fragments of HIV-1 RNA derived from the 5' UTR containing the Psi packaging signal. In this manner, the number of Gag molecules assembling around each RNA molecule, as well as the rate constants for each step of assembly, will be determined. A series of assembly-defective Gag mutants will also be examined; the results will identify which assembly steps are impaired in each mutant. Overall, these single-molecule experiments are expected to reveal the roles of Gag-RNA and Gag-Gag interations during early steps of Gag assembly. They will also establish a new method to quantitatively dissect a key process in the HIV-1 life cycle. As a complement to these in vitro studies, I will also examine Gag-containing complexes formed in cells. I will develop methods to count the number of Gag-GFP monomers in each complex, based on single-molecule intensity distribution analysis and/or photobleaching step counting. These results will reveal the Gag stoichiometry in different complexes and help to test models of Gag assembly in vivo.

 

Robin Willenbring, Ph.D. (06/01/18 - Present)       Mentor: Linda Sherman, Ph.D.

Defining the role of the proautoimmune risk allele, PTPN22 1858 C>T, in controlling and regulating chronic viral infection and subsequent T cell exhaustion

To elucidate the role of PTPN22 during chronic viral infection and T cell exhaustion, we will employ the well-established model of persistent viral infection, LCMV-cl13, in our aforementioned mice. Following infection, we will determine disease progression (weight and survival), viral load in serum and target organs at acute and chronic time points, and circulating and target organ anti-viral immune response (cytokine, innate cell, and adaptive cell). To determine T cell exhaustion, we will quantify the expression of inhibitory receptors on both circulating and organ specific T cells during chronic infection with LCMV-cl13. Additionally, we will isolate T cells and employ re-stimulation assays to assess cytokine production and proliferation. Next, through a series of adoptive transfer experiments, we will define which R619W-wielding immune cells are necessary and/or sufficient for proper viral control and T cell exhaustion. Completion of this study will detail the role of PTPN22 during anti-viral immune response and T cell exhaustion, providing critical groundwork for future studies defining pathogenesis associated with this gene.

 

Kip Hermann, Ph.D (12/1/16 - Present)                  Mentor: Bruce Torbett, Ph.D.

Identification of human hematopoietic stem cell lentiviral vector restriction pathways in order to improve the efficiency of lentiviral-mediated gene transfer to hematopoietic stem cells 

Inefficient gene transfer of hematopoietic stem cells (HSCs) by lentivirus has hindered the clinical application of many therapies.  We are investigating various small molecules that have been found to have an effect on lentiviral transduction of HSCs and the underlying mechanism of these effects.  Our goal is to improve lentiviral transduction of HSCs by better understanding and manipulating the pathways revealed from these small molecule studies.

 

Jordan Woehl, Ph.D. (6/20/17 - Present)                 Mentor: Dennis Wolan, Ph.D.

Identification, quantitation, and biochemical analysis of proteases secreted into the distal gut targeted for inhibition by host anti-proteolytic proteins

Through an optimized liquid chromatography tandem mass spectrometry (LC-MS/MS) metaproteomics approach on an adoptive T cell transfer murine model of chronic colitis, we have supported decades-old research that identified an increase in general proteolytic activity with fecal extracts of colitic mice and humans.  Moreover, we observed a correlated increase in host anti-proteolytic proteins (APPs) that we hypothesize are secreted into the gut lumen to quench aberrant proteolytic activity.  The exact molecular mechanism(s) causing inflammation in the gut remain poorly understood, so there is an urgent need to establish which host and microbial proteases are targeted by host APPs and if these same proteases, a different subset of proteases, or a combination of both, promote colitis.  We will elucidate the host and/or microbiome protein targets of six APPs previously identifiied among the most abundantly produced host proteins in response to distal gut inflammation and are known to collectively target proteases from the serine, cystine, and metallo subfamilies.  Ultimately, we hope to address the biological mechanism(s) of how altered proteolytic activity promotes host inflammation and assess the therapeutic potential of selective protease inhibition on inflammatory bowel diseases.

 
  Former Trainees and Current Positions (1999-2019)  
 

Jacob Milligan, Ph. D. (Saphire Lab) - Postdoctoral Fellow, La Jolla Institute for Immunology

Steffen Bernard, Ph.D. (Wilson Lab) - Sr. Research Associate, Celgene Corp., San Diego

Cari Kessing, Ph.D. (Valente Lab) - Research Scientist, GlaxoSmithKline

Nina Timberlake, Ph.D. (Torbett Lab) - Research Scientist, Poseida Therapeutics, San Diego

Brett Marro, Ph.D. (Oldstone lab) - Research Associate, Scripps, San Diego

Robert Kirchdoefer, Ph.D. (Saphire Lab) - Research Associate, Scripps, San Diego

David Guimond, Ph.D. (Mowen Lab) - Scientist, Receptors/Celgene, San Diego

Brian Adair, Ph.D. (Yeager Lab) – Instructor, Medicine, Massachusetts General Hospital

Michael Baksh, Ph.D. (Finn Lab) - Research Scientist, Georgia Institute of Technology

Jason Botten, Ph.D. (Buchmeier Lab) – Assistant Professor, Univ. of Vermont

Amy Brideau-Andersen, Ph.D. (Chisari Lab) – Staff Scientist I, Maxygen

Emily Burke, Ph.D. (Buchmeier Lab) – Graduate Advisor UCSD Career Services Center

Ryan Burnett, Ph.D. (Gottesfeld Lab) – Research Scientist, Tocagen, Inc.

Althea Capul, Ph.D. (de la Torre Lab) – Associate Biosafety Officer, NIH

Max Chang, Ph.D. (Torbett Lab) – Programmer Analyst, UC San Diego

Jill Chrencik, Ph.D. (Kuhn Lab) – Protein Crystallographer and Biochemist, Merck

Barney Collins, Ph.D. (Wilson Lab) –  Scientist, Plex Pharmaceuticals

Jodi Connolly, Ph.D. (Nemerow Lab) – Patent Agent, Klarquist Sparkman, LLP

Christopher Cornell, Ph.D. (Whitton Lab) – Scientist, Allergan

Cromwell Cornillez-Ty, Ph.D. (Kuhn Lab) – Investment Advisor Rep., STEM Financial LLC, San Diego

Amy Cullinan, Ph.D. (Manchester Lab) – Scientist, Invitrogen

Shrimati Datta, Ph.D. (Sarvetnick Lab) – Project Coordinator, CDPH, San Francisco

Jose Garcia, Ph.Dh (Gallay Lab– Research Scientist II, Roka Bioscience

Megan Guelker, Ph.Dh (Johnson Lab)– Sr. Product Manager, Abott

Michael Giffin, Ph.D. (Torbett Lab) - Scientist, Amgen, Inc. Thousand Oaks, CA

Jennifer Head, Ph.D. (J. de la Torre Lab) – Research Scientist, AutoGenomics Inc.

Yang Hong, Ph.D. (Elder Lab) - Scientist, BioVision, Inc.

Ashley Horton, Ph.D. (Schneemann Lab) – Pharmacogenetics Scientiest, Millennium Laboratories, San Diego

Christopher Kimberlin, Ph.D. (Ollmann-Saphire Lab) – Senior Scientist, Pfizer

Kevin Koehntop, Ph.D. (Yeager Lab) – Unknown

Claire Levy, Ph.D. (Vogt Lab) –  Staff Research Associate, UC San Francisco

Crystal Moyer, Ph.D. (Newerow Lab) – Research Scientist, Mapp Biopharmaceutical

Samia Naccache, Ph.D. (Nemerow Lab) - Technical Microbiology Director, LabCorp Diagnostic Laboratories

Amy Odegard, Ph.D. (Johnson Lab) – Assistant Professor, University of Puget Sound, Tacoma, WA

Bruno Sainz, Jr., Ph.D. (Chisari Lab) – Staff Scientist, Autonoma Univesity of Madrid, Spain

Theresa Sample, Ph.D. (Stout Lab– Patent Agent, Ionis Pharmaceuticals

John Teijaro, Ph.D. (Oldstone Lab) - Asst. Professor, IMS Dept, TSRI

Joie Bernard-Trifilo, Ph.D. (Oldstone Lab) – Regional Medical Liaison, Amgen

Susan Uprichard, Ph.D. (Chisari Lab) – Assistant Professor, University of Illinois

Shuzo Urata, Ph.D. (de la Torre Lab) - Assistant Professor, Nagasaki University, Japan

Christopher Wiethoff, Ph.D. (Nemerow Lab) – Assistant Professor, Loyola University

Eugene Wu, Ph.D. (Johnson Lab) – Research Associate, Duke University

Priscilla Yang, Ph.D. (Chisari Lab) – Assistant Professor, Harvard Medical School

Jinyun Yuan, Ph.D. (Torbett Lab) – Assist. Research Professor, Saint Louis University