Training Grant Recipients


 

TSRI Current Trainees (2016-2017)

 
 

 

Cari F. Kessing, Ph.D. (06/01/15-present)         Mentor: Susana Valente, Ph.D.

 

Determining molecular mechanisms of HIV transcriptional shutdown by a novel Tat inhibitor,  didehydro-Cortistatin A, in a novel primary cellular model of latency

My project focuses on an alternative approach to the “shock and kill” strategy for HIV eradication using a Tat inhibitor, didehydro-Cortistatin A (dCA), to drive the residual transcription in the latent reservoir into deep latency. dCA has been found to reduce ongoing viral transcription in several HIV latency models and establish a state of deep latency in cell lines from which viral reactivation is greatly diminished. Currently, my results suggest that long-term treatment with dCA in combination with ARV treatment in primary HIV+ human CD4+ T cells inhibits transcription and residual HIV replication to such a degree that even after treatment cessation HIV-1 RNA transcripts are not detected over tim

 

Publications:

 1. Mousseau, G., Kessing C.F., Fromentin, R., Trautmann, L., Chomont, N., Valente, S.T. (2015). The tat inhibitor didehydro-cortistatin A prevents HIV-1 reactivation from latency. MBio. 6(4). PMCID: PMC4495168

 

 

Steffan Bernard, Ph.D. (11/1/16 - present)   Mentor: Ian Wilson, Ph.D.

 

Structural investigation of HIV broadly neutralizing antibodies elicited in human Ig-knockin mice.

The N332 supersite of the HIV envelope glycoprotein is a common epitope for naturally occurring broadly neutralizing antibodies (bNAbs) and therefore, the epitope represents a promising target for site-specific vaccine strategies.  Recently, in vivo experiments with human antibody knockin mice demonstrated the utility of designed immunogens for targeting a specific site and guiding somatic mutation through a sequential boosting protocol, resulting in the production of broadly neutralizing antibodies.  I am using biophysical methods, including X-ray crystallography, to investigate how breadth can be achieved within this immunization platform.  By comparing these antibodies to previously studied bNAbs I will further characterize the features that contribute to neutralization breadth and inform the development of the next generation of immonogens.

 

 

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.


 

Jacob Milligan, Ph.D. (6/26/17 - present)                Mentor: Erica Saphire, Ph.D.

 

Structural studies of ebolavirus glycoproteins and cross-reactive antibodies directed against them

Viruses of the genus Ebolavirus can cause severe and often fatal hemorrhagic fever in humans and other mammals.  Of the five ebolaviruses, three are known to cause lethal infections in humans: Ebola virus, Sudan virus, and Bundibugyo virus.  There are currently no approved treatments or vaccines for any of the ebolaviruses, though several candidates are currently in clinical trials.  However, the most promising vaccine candidate is specific to only the Ebola virus and offers no protection against Sugan virus and Bundibugyo virus.  Thus, the need for a pan-ebolavirus vaccine remains unmet.  In recent years, several antibodies have been described that offer protection against all three of these viruses, though the structural basis for their cross-reactivity remains largely unknown.  The goal of my project is to determine high-resolution X-ray crystal structures and/or cryo-EM structures of ebolavirus glycoproteins in complex with these cross-reactive antibodies in order to facilitate structure-based antigen design and optimization for use in pan-ebolavirus vaccines.

 

 

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 (1999-2015)  
 

 

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

Brett Marro, Pd.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)-Group Technical Director, The Finn Research Group, Georgia Tech. Georgia

Jason Botten, Ph.D. (Buchmeier Lab) – Assistant Professor, Adjunct, TSRI

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) – Biosafety Program Manger, Maryland

Max Chang, Ph.D. (Torbett Lab) – Scientific Programmer II, Salk Institute for Biological Studies

Jill Chrencik, Ph.D. (Kuhn Lab) – Staff Scientist, Receptos Inc. San Diego

Barney Collins, Ph.D. (Wilson Lab) –  Research Associate, TSRI

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) – Analyst at Rady School of Management, San Diego

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

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

Jose Garcia, Ph.D (Gallay Lab– Principal Investigator, Infectious Diseases, US Navy, Washington D.C.

Megan Guelker, Ph.D (Johnson Lab)–Marketing Manager, CTK Biotech, San Diego 

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

Jennifer Head, Ph.D. (J. de la Torre Lab) – Research Associate, TSRI

Yang Hong, Ph.D. (Elder Lab) Director of R&D Department, SuZhou, China

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

Christopher Kimberlin, Ph.D. (Ollmann-Saphire Lab) –Senior Fellow, UCSF

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

Claire Levy, Ph.D. (Vogt Lab) –  Staff Scientiest, DxRx, Inc. San Francisco

Crystal Moyer, Ph.D. (Newerow Lab) – Research Associate, TSRI

Samia Naccache, Ph.D. (Nemerow Lab) - Senior Fellow, UC San Francisco

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– Research Associate, TSRI

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

Joie Bernard-Trifilo, Ph.D. (Oldstone Lab) – Scientist, Millipore (formerly Chemicon)

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