Training Grant Recipients


 

TSRI Current Trainees (2019-Present)

 
 

Arthur Kim, Ph.D. (2/16/2021 - Present)          Mentor: John Teijaro, Ph.D. & Benjamin Cravatt, Ph.D.

Chemoproteomic Profiling of the Host Landscape During SARS-COV-2 Infection

SARS-CoV-2 is a global health threat that has affected >100 million individuals worldwide and has resulted in >2 million deaths. Clinical disease in infected individuals can vary from asymptomatic infection to cytokine storm syndrome, multiple organ failure, and death. The recent deployment of COVID-19 vaccines has mitigated the risk of severe COVID-19 disease; however, the emergence of new SARS-CoV-2 variants could severely compromise vaccine efficacy. The identification of host factors required for SARS-CoV-2 pathogenesis can inform translational efforts to create additional countermeasures that reduce COVID-19 morbidity and mortality. The basis and innovation of the chemoproteomic platform will be the use of cysteine-reactive stereoisomeric compounds developed in the Cravatt laboratory. Similar ligands, which covalently modify cysteine residues, have previously been used to identify the druggable proteome in T cells and lung carcinoma cells. The stereoisomeric compounds, which consist of matched pairs that differ in stereochemistry, will be screened in physiologically relevant cells for their ability to i) reduce SARS-CoV-2 infection levels and ii) decrease the host inflammatory response. Positive hits from this phenotypic screen will be prioritized for competitive activity-based protein profiling (ABPP) and tandem mass tagged mass spectrometry to identify protein targets. A key advantage of this approach is the ability to identify stereoselective host factor interactions that modulate SARS-CoV-2 replication and/or induction of cytokine storm.

 

Winston Stauffer, Ph.D. (11/1/20 - Present)     Mentor: Philippe Gallay, Ph.D.

Exploring Novel Treatments for SARS-CoV-2 Infection

This project explores novel therapeutics for the treatment of SARS-CoV-3 infection. To address the urgent need for such treatments, the goal will be to examine therapeutics that are already being considered by the FDA for use in the treatment of human disease.

One branch of the study will involve treatment of SARS-COV-2 infection with cyclophilin inhibitor compounds. Host cyclophilins, acting as protein chaperones, are known to be involved in various aspects of the lifecycles of multiple virus families; their inhibition has been shown to be effective in halting viral infection. A pan-cyclophilin inhibitor compound was a candidate for treatment of HCV infection and has recently been found to prevent the replication of multiple coronaviruses in cell culture. This branch will examine a related compound, CRV-431 in SARS-CoV-2 infection in cell culture and in mice.

Another project branch will take advantage of the RNA polymerase SARS-CoV-2 uses to amplify its genome post-infection. This polymerase generates sub-genomic negative-sense copies of the viral RNA, and then converts those copies back to positive-sense RNA, which can then be translated by host ribosomes. This project aims to intorduce negative-sense RNA encoding a fragment of diphteria toxin, which will only be recognized by the viral polymerase and will only be translated in cells that are infected. This will lead to the targeted destruction of only those host cells which have the virus, preventing infection of other cells. This project branch likewise has in vitro and in vivo aspects and may have additional applications outside coronavirus infection.

 

Areeje Almasary, Ph.D. (05/01/20 - Present)       Mentor: Mansun Law, Ph.D.

B Cell Responses in Chronic Hepatitis B Infection

Recent studies on the host immune response in chronic HBV infection discovered that B cells in chronic HBV infection adopt an atypical memory phenotype (atMBC) and theye are defective in producing antibodies. The atMBC have dampened receptor signaling, unable to differentiate into antibody producing cells upon simulation in vitro, and have elevated expression of inhibitory receptor FcRL5 and PD-1. In my prosposed studies, I will investigate B cells in chronic HBV patients to understand the mechanism of immune suppression. The results will be useful for the development of novel strategies to restore antibody response in chronic HBV patients. To study anti-HBV B cell responses in HBV patients, HBsAg-specific B cells in patient blodd and liver tissues will be isolated and studied for their functions and responses to in vitro stimulation.

 

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

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

Mesoscopic Simulation of the Mature HIV Capsid

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.

 
  Former Trainees and Current Positions (1999-2021)  
 

Robin Orozco, Ph.D. (Sherman Lab) - Postdoc Associate, Scripps Research CA

Laura Healy, Ph.D. (Griffin and Mosnier Lab) - Manager, Clinical Devt/Medical Writing, Sorrento Therapeutics

Raymond Pauszek, Ph.D. (Millar Lab) - Workflow Software Engineer, LUMICKS, Netherlands

Jordan Woehl, Ph.D. (Wolan Lab) - Protein Scientist, IAVI

Kip Hermann, Ph.D. (Torbett Lab) - Research Scientist, Salk Institute

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) - Asst. 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 Servoces 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 Franciscisco

Jose Garcia, Ph.D. (Gallay Lab) - Research Scientist II, Roka Bioscience

Megan Guelker, Ph.D. (Johnson Lab) - Sr. Product Manager, Abott

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

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

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

Ashley Horton, Ph. D. (Schneemann Lab) - Pharmacogenetics Scientist, Millenium 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. (Nemerow Lab) - Research Scientist, Mapp Biopharmaceutical

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

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

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

Therasa 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) -  Asst. Professor, University of Illinois

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

Christopher Wiethoff, Ph.D. (Nemerow Lab) -  Asst. Professor, Loyola University

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

Priscilla Yang, Ph.D. (Chisari Lab) - Asst. Professor, Harvard Medicine School

Jinyun Yuan, Ph. D. (Torbett Lab) - Asst. Research Professor, Saint Louis University