Antiretroviral Discovery, Evaluation and Application Research (ADEAR) Training Program

Applications, which include the following documents, must be submitted electronically through the link below. Please contact Chelsee McFarland at chelsee.mcfarland@cuanschutz.edu with any questions.

Application Items:

1. Letter of interest from candidate, including statement of interest in academic career and commitment to pursuing a career in HIV-related research, and training plan during the proposed 2-year funding period. Limit 2 pages.
2. CV, resume, or NIH biosketch of the applicant.
3. NIH biosketch of the mentor including the current funding.
4. Letters of recommendations (4 total) including 1 from proposed postdoctoral mentors (combined if co-mentors) for the proposed training project.
5. Career Development Plan (Limit 1 page).
6. Project description from candidate (font Arial 11, ½” margins). Limit 3 pages. (a) Specific aims/hypotheses,  (b) Background, (c) Brief experimental approach, (d) Brief Timeline for research activity and expected end products of your research (spanning 2 possible years of funding).
7. References (Limit 1 page, not inclusive of project description).
8. Training Responsible Conduct of Research (for specific requirements see: https://www.niaid.nih.gov/research/responsible-conduct-research-training). Limit 1 page.
   

a. Format: must include face-to-face (via zoom or in person depending on the institutional guidelines) discussions among trainees (case studies).

b. Subject Matter.

c. Faculty Participation: training faculty are highly encouraged to participate in formal/informal instruction.

d. Duration of Instruction: at least 8 contact hours of instruction (semester-long series are preferred).

e. Frequency of Instruction: at least once in each career stage and/or every 4 years.

Awards:

• The NIH study section format will be used to rank the applications.

Co-Program Director: Thomas Campbell, M.D., Professor of Medicine and Microbiology (UC-AMC).  Dr. Campbell’s research focuses on clinical investigations of antiretrovirals for treating HIV/AIDS and he has worked collaboratively with investigators from diverse disciplines and other institutions.  Research interests include gender differences in response to antiretroviral therapy, the effects of simplified dosing on adherence to antiretrovirals, the consequences of transmitted and acquired antiretroviral drug resistance, the role of malnutrition in response to antiretrovirals, and the effects of co-infections, chronic inflammation and immune activation in resource limited settings. 

Email: THOMAS.CAMPBELL@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/4502

Co-Program Director: Mamuka Kvaratskhelia, Ph.D., Professor of Medicine (UC-AMC). Dr. Kvaratskhelia is a biochemist, pharmacologist, and molecular virologist who has developed a very interactive research program with both basic science and translational components. He has been at the forefront of developing and elucidating the mode of action of a completely novel class of antiviral agents termed allosteric HIV-1 integrase inhibitors for their potential clinical application.

Email: MAMUKA.KVARATSKHELIA@CUANSCHUTZ.EDU

Faculty Website: https://medschool.cuanschutz.edu/infectious-diseases/faculty/id-faculty/mamuka-kvaratskhelia

Associate Program Director: Kristine Erlandson, M.D., Associate Professor of Medicine, Division of Infectious Diseases (UC-AMC).  Dr. Erlandson investigates the complications of aging during antiretroviral treatment, specifically the mechanisms through which chronic HIV infection and the dysregulated inflammatory response leads to early frailty and physical function decline despite otherwise successful antiretroviral therapy.  She has identified strong associations between markers of inflammation and immune activation with frailty. Recent work evaluated the effects of 24 weeks of moderate vs high intensity exercise on physical function, as mediated through changes in biomarkers including those of inflammation (IL-6, TNF-α), immune activation (sCD14, sCD163), and insulin like growth factor (IGF)-1 pathway.  Dr. Erlandson is also PI of an R01 grant to investigate the impact of pitavastatin on muscle function and intramuscular fat in people with HIV on antiretroviral therapy and she is developing a new project to investigate the mechanisms of weight gain during treatment with integrase inhibitors. 

Email: KRISTINE.ERLANDSON@CUANSCHUTZ.EDU 

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/6113 

Lisa Abuogi, M.D., Assistant Professor of Pediatrics, Section of Infectious Diseases (UC-AMC). Dr. Abuogi’s research focuses on implementation science to improve HIV prevention and treatment in resource limited settings. She has conducted research on the incidence and prevalence of TB co-infection among HIV infected children in Kenya. She is currently PI for a large multi-site community randomized study to maximize retention and adherence amongst women and infants in the context of Option B+ in Kenya. This includes the evaluation of a large scale multi-component intervention to rapidly improve PMTCT services in western Kenya, assessment of family testing to identify HIV-infected children, and assessment of delays in treatment initiation for HIV-infected children.  

Email: Lisa.Abuogi@childrenscolorado.org

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/21129

Ramesh Akkina, Ph.D., Professor of Microbiology, Immunology and Pathology (CSU).  Dr. Akkina’s research focus is in humanized mouse models for evaluation of new approaches to HIV treatment and prevention.  He has over 35 years of experience in both basic and applied infectious disease research in both veterinary and medical fields.  He was instrumental in refining several gene transfer protocols and chiefly responsible for developing the SCID-hu mouse model with transplanted human tissue for stem cell reconstitution and gene therapy. His team was among the first to pseudotype an HIV-based lentiviral vector with the VSV-G envelop and achieve high efficiency gene transduction into CD34 hematopoietic progenitor cells.  His laboratory has adapted the new RAG-hu mouse model with the capacity for multilineage human hematopoiesis and human immune responses for studies of HIV infection and pathogenesis.  Dr. Akkina serves as a mentor for trainees in the use of animal models in HIV treatment and prevention research, the design and utilization of siRNAs/RNAi for gene knock-down, use of retro-and lentiviral vectors for gene transfer and therapy, derivation of hematopoietic cells from human embryonic stem cells and techniques for gene transfer into hematopoietic stem cells. 

Email: Ramesh.Akkina@colostate.edu 

Faculty Website: http://www.cvmbs.colostate.edu/DirectorySearch/Search/MemberProfile/CVMBS/3131/Akkina/Ramesh

Peter Anderson, Pharm.D., Professor of Pharmaceutical Sciences (UC-AMC).  Dr. Anderson’s research interest is clinical pharmacology of antiretroviral agents.  His laboratory has expertise in measuring, interpreting, and analyzing extracellular and intracellular antiretroviral drug concentrations in vivo.  He investigates pharmacokinetic considerations for antiviral therapy including biological factors that alter pharmacokinetics and the implications of altered pharmacokinetics on drug efficacy and toxicity.  An ongoing study of the cellular pharmacology of tenofovir and emtricitabine in HIV-negative and HIV-positive persons to inform optimal dosing strategies for HIV treatment and prophylaxis is an example of a project that could provide a research training opportunity for an ADEAR trainee.

Email: PETER.ANDERSON@CUANSCHUTZ.EDU

Faculty Website: https://pharmacy.cuanschutz.edu/about-us/faculty-and-staff-directory/peter-anderson

Jose Castillo-Mancilla, M.D., Associate Professor of Medicine, Division of Infectious Diseases (UC-AMC).  Dr. Castillo-Mancilla is a translational researcher focused in applied antiretroviral clinical pharmacology with emphasis on antiretroviral drug adherence, optimization of current antiretroviral therapies, pharmacogenomics and pre-exposure prophylaxis (PrEP). He is the lead investigator for ACTG study A5359, an ongoing multi-site study aiming at evaluate the efficacy of long-acting antiretrovirals on non-adherent individuals. Dr. Castillo’s research interests also include antiretroviral treatment in Hispanics, including research to address an ongoing need for evaluation and development of outreach programs for Hispanics in order to reduce HIV incidence in this population and improve access to treatment.

Email: JOSE.CASTILLO-MANCILLA@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/18367

Chaoping Chen, Ph.D., Associate Professor of Biochemistry and Molecular Biology (CSU).  Dr. Chen’s laboratory uses a cell-based assay to study autoprocessing of HIV protease precursors as a rapid tool for phenotype assessment to evaluate the effects of mutations outside of the protease coding region on protease phenotype.  Potential projects for ADEAR trainees include laboratory based investigations to characterize protease autoprocessing phenotypes from clinical specimens obtained from patients on protease inhibitor based therapies and correlations between autoprocessing phenotype and virologic response to protease inhibitors. 

Email: Chaoping.Chen@colostate.edu

Faculty Website: https://www.bmb.colostate.edu/about/people/person/?id=B7AF5E0E1EC353F92840DA5A9246D31C&sq=t

Christopher DeSouza, Ph.D., Professor of Integrative Physiology (UCB).  Dr. DeSouza is Co-Director of the CCTSI site on the Boulder campus.  His laboratory studies the effects of cardiovascular and metabolic risk factors as well as lifestyle interventions on vascular endothelial cell function in adult humans.  Specific areas of interest include:  regulation of endothelial vasomotor regulation; endothelial fibrinolytic control; plasma proteomic markers of endothelial function; endothelial progenitor cell function; and the effects of exercise and antioxidant supplementation on endothelial health and function.  Dr. DeSouza’s has previously studied the effects of HIV infection and antiretroviral therapy on vascular endothelial function to gain insight into potential mechanisms responsible for the increased cardiovascular disease burden in HIV-seropositive adults.  An ongoing project is determining the effects of short duration sleep on vascular endothelial cell function in HIV-1 treatment and will provide training opportunities in clinical and translational research for trainees interested in cardiovascular complications of antiretrovirals. 

Email: desouzac@colorado.edu

Faculty Website: https://www.colorado.edu/iphy/people/professors/chris-desouza

Edward N. Janoff, M.D., Professor of Medicine, Division of Infectious Diseases (UC-AMC).  Dr. Janoff studies the induction of systemic and mucosal responses to Streptococcus pneumoniae infection and vaccination during antiretroviral therapy, the molecular basis for capsule-specific antibody responses (VH gene diversity and mutational pattern), and the functional activity of these human antibodies.  His team characterizes mucosal responses to S. pneumoniae in the lung and to HIV in the intestine, reproductive tract, and in breast milk.  Each study is supported by a field site in Africa (Uganda, Burkina Faso, Botswana and South Africa) with collaborators from these African nations, the U.S. and Europe. Dr. Janoff serves as a mentor for ADEAR trainees who are interested in clinical and basic laboratory approaches to study host-HIV interactions at mucosal surfaces during antiretroviral therapy.   

Email: EDWARD.JANOFF@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/15947

Jennifer Kiser, Pharm.D., Associate Professor of Pharmaceutical Sciences (UC-AMC).  Dr. Kiser is an antiviral clinical pharmacologist who conducts concentration-effect and drug-drug interaction studies with antiviral drugs.  Dr. Kiser’s recent and ongoing projects include evaluations of the plasma and intracellular pharmacokinetics of tenofovir, exploration of a renal mechanism for the drug interaction between tenofovir and lopinavir/ritonavir, concentration-guided lopinavir/ritonavir dosing in HIV-infected pregnant women, assessment of interactions with HIV protease inhibitors and HMG-CoA reductase inhibitors (statins), and in vitro determinations of the potential for intracellular drug-drug interactions between entecavir and ribavirin.  Dr. Kiser serves as mentor for ADEAR trainees who are interested in studying the pharmacology of antiretroviral drugs. 

Email: JENNIFER.KISER@CUANSCHUTZ.EDU

Faculty Website: https://pharmacy.cuanschutz.edu/about-us/faculty-and-staff-directory/jennifer-kiser

Laurel Lenz, Ph.D., Professor of Immunology and Microbiology (UC-AMC). Dr. Lenz’s research focuses on better-understanding of how innate immune responses are regulated and dysregulated in the context of health and disease.  A recent collaboration between Drs. Lenz and Weinberg found that HIV-uninfected infants born to HIV infected mothers, and exposed to antiretroviral drugs in utero, had altered NK cell proportion, phenotype, and function with dysregulation of NK cell cytotoxicity at birth including reduced IFNγ and perforin production.  These findings provide an immunologic mechanism to explain why HIV-exposed infants have increased susceptibility to infection.  Dr. Lenz serves as a mentor for ADEAR trainees who are interested in investigating the effects of antiretrovirals used for HIV treatment or prevention on innate immune responses.

Email: LAUREL.LENZ@CUANSCHUTZ.EDU

Faculty Website: https://medschool.cuanschutz.edu/immunology-and-microbiology/faculty/lenz

Myron J. Levin, M.D., Professor of Pediatrics and Medicine, Section of Infectious Diseases (UC-AMC).  Dr. Levin’s research interests are antiviral therapy in children, adolescents and pregnant women and in especially the immunology of vaccines.  He is Co-PI of the IMPAACT network Clinical Research Site at Children’s Hospital Colorado.  He is collaborating with Drs. Campbell and Castillo-Mancilla on a randomized clinical trial of early antiretroviral initiation in adolescents and adults with newly diagnosed HIV infection.  Potential research projects for ADEAR trainees include investigations of novel antiviral drugs to treat and prevent HIV infection in children and adolescents, and prevention of mother-to-child transmission of HIV, and evaluation of the effects of antiretroviral therapy on immune responses to vaccines.

Email: MYRON.LEVIN@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/18048

Catherine Lozupone, Ph.D., Assistant Professor of Medicine, Division of Bioinformatics and Personalized Medicine (UC-AMC).  Dr. Lozupone’s studies the factors that shape human microbiome composition in health and disease and investigates the functional consequences of compositional differences, both in terms of the biological/metabolic properties of individual bacteria and host interactions.  She was the primary developer of the UniFrac algorithm for comparing microbial diversity among many samples using phylogenetic information, and a contributor to the QIIME software package. In recent and ongoing R01 funded research she investigated whether gut microbiota composition of individuals with HIV on antiretroviral therapy is linked with metabolic disease; the extent to which microbiome compositional differences are driven by a loss of bacteria that induce CD4+ T regulatory cells; and the interaction between diet and disease in HIV infected subjects in the US and in Zimbabwe. Under her mentorship, trainees can use 16S rRNA analysis, comparative genomics, and meta-analysis to study microbiome changes with HIV-infection, and the relationships between the gut microbiome, chronic inflammation and susceptibility to HIV infection. 

Email: CATHERINE.LOZUPONE@CUANSCHUTZ.EDU

Faculty Websites: https://som.ucdenver.edu/Profiles/Faculty/Profile/21289  and https://medschool.cuanschutz.edu/biomedical-informatics-and-personalized-medicine/labs/lozupone-lab    

Elizabeth McFarland, M.D., Professor of Pediatrics, Head, Section of Infectious Diseases (UC-AMC).  Dr. McFarland is the Director of the Children’s Hospital HIV Program which serves HIV-affected infants, children, youth, pregnant women, and families.  She is Co-PI of the IMPAACT network Clinical Research Site at Children’s Hospital Colorado.  Dr. McFarland studies the maturation of cell-mediated immune responses in both HIV-exposed and HIV-infected infants, immune responses to HIV vaccines in HIV-exposed newborns, the role of cytotoxic T-lymphocytes in the pathogenesis of congenitally acquired HIV infection, pediatric HIV clinical trials of antiretroviral therapy and vaccines.  Potential research training projects for ADEAR mentees include evaluation of cellular immune response in HIV-uninfected infants and children born to HIV-infected mothers and exposed to antiretrovirals in utero. 

Email: BETSY.MCFARLAND@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/10199

Brent Palmer, Ph.D., Associate Professor of Medicine, Division of Allergy and Clinical Immunology (UC-AMC).  Dr. Palmer studies the effects of HIV infection on systemic and mucosal immunity and interactions between commensal microbiota in the gut and lung and the immune system during antiretroviral therapy. His work has demonstrated that HIV-1 replication impacts T cell function by triggering the overexpression of inhibitory receptors, such as PD-1, that induce T cell exhaustion and that that exhaustion can be reversed, and HIV-1 replication reduced, by PD-1 pathway blockade using HIV-infected humanized mouse models.  He serves as the Director of the ACI/ID Flow Cytometry facility and the ClinImmune Clinical Immunology lab also brings with access to state-of-the-art flow cytometric instrumentation. ADEAR trainees will have opportunities for mentored research in the microbiome and mucosal immunity in the gut and the interaction between these mucosal compartments and how they influence one another during HIV treatment and in high-risk men who have sex with men. 

Email: BRENT.PALMER@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/3527

Eric Poeschla, M.D., Professor of Medicine, Head, Division of Infectious Diseases (UC-AMC).  Dr. Poeschla is the Tim Gill Professor of Medicine.  His laboratory investigates basic aspects of retroviral replication, host innate immunity to retroviruses, and retroviral disease pathogenesis including host cell dependency factors, cell-intrinsic innate immunity/restriction factors, integration, and accessory protein function. He contributed foundational work on the role of LEDGF as both HIV integration cofactor and an HIV-1 host dependency factor.  Dr. Poeschla will provide ADEAR trainees with mentorship in the molecular mechanisms of HIV related the development of new strategies to treat HIV.

Email: ERIC.POESCHLA@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/22141

Mario Santiago, Ph.D., Associate Professor of Medicine, Division of Infectious Diseases (UC-AMC).  Dr. Santiago’s laboratory focuses on defining innate antiretroviral mechanisms and their impact on humoral and cell-mediated immune responses in vivo, using three complementary biological systems. First, using genetic tools, he investigates basic innate mechanisms that influence the outcome of pathogenic Friend retrovirus infection in mice.  Second, using engineered molecular clones of simian immunodeficiency virus, he investigates the immunological impact of attenuating encoded viral immune antagonists. Finally, using biological samples from human populations resistant or susceptible to HIV, he studies immunogenetic properties that regulate innate HIV resistance.  Dr. Santiago serves as a mentor for ADEAR trainees who seek laboratory-based studies of innate resistance to HIV infection and its role in HIV prevention and treatment. 

Email:  MARIO.SANTIAGO@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/593

Sarah Sawyer, Ph.D., Associate Professor of Molecular, Cellular and Developmental Biology (UCB).  Dr. Sawyer studies viral restriction factors and viral entry receptors by combining laboratory research in virology with tools from molecular evolution, population genetics, bioinformatics, and genomics.  Her work on HIV-1 spans more than a decade, and has focused on cellular-level evolutionary and functional interactions between virus and host. Dr. Sawyer provides mentored research opportunities for ADEAR trainees who wish to study the evolution of HIV-1 in the context of HIV treatment and prevention. 

Email: ssawyer@Colorado.EDU

Faculty Website: https://www.colorado.edu/mcdb/sara-sawyer

Raul Torres, Ph.D., Professor of Immunology and Microbiology (UC-AMC).  Dr. Torres investigates the mechanisms by which B lymphocytes develop and subsequently mount antibody responses to foreign antigens and pathogens.  His research has focused on understanding how the distinct B cell populations that exist in humans and mice act in concert to provide humoral immunity including the contribution of marginal zone B cells to the antibody response to HIV.  Ongoing work is investigating how auto-reactive B cell receptors can also recognize epitopes on pathogens and mount protective antibody responses against both bacteria and viruses, including HIV.  Dr. Torres will serve as a mentor for ADEAR trainees who seek mentorship in the development and evaluation of antibody-based approaches for HIV prevention and treatment.

Email: RAUL.TORRES@CUANSCHUTZ.EDU

Faculty Website: https://medschool.cuanschutz.edu/immunology-and-microbiology/faculty/torres

Linda van Dyk, Ph.D., Professor Immunology and Microbiology (UC-AMC).  Dr. van Dyk’s research focus is characterization of host-pathogen interactions in gammaherpesvirus infection, with primary emphasis on latency and reactivation.  Her laboratory studies the effects of tumor suppressors on chronic viral infection, and the effects of chronic infection on tumor suppressor function.  She serves as a mentor for ADEAR trainees who wish to study the virological mechanisms by which herpesvirus contribution to chronic inflammation during antiretroviral treatment of HIV infection. 

Email: LINDA.VANDYK@CUANSCHUTZ.EDU

Faculty Website: https://medschool.cuanschutz.edu/immunology-and-microbiology/faculty/van-dyk

Schuyler Van Engelenburg, Ph.D., Assistant Professor of Biological Sciences (DU). Dr. Van Engelenburg completed his postdoctoral training at NIH where he investigated how a single HIV-1 particle is formed in an infected cell using single molecule imaging approaches.  His current research uses advanced superresolution microscopy techniques, protein chemistry and probe development, and computational image analysis to quantitatively understand the cellular, biochemical, and genetic drivers of HIV-1 assembly and to construct molecularly accurate spatial and temporal models for HIV biogenesis for the purpose of developing new antiviral therapies targeting the assembly stage of the HIV infection cycle.  Dr. Van Engelenburg serves as as mentor for ADEAR trainees interested in laboratory-based training to discover or evaluate inhibitors of HIV assembly.

Email: schuyler.vanengelenburg@du.edu

Faculty Website: https://science.du.edu/about/faculty-directory/schuyler-van-engelenburg

Adriana Weinberg, M.D., Professor of Pediatrics and Medicine, Section of Infectious Diseases (UC-AMC).  Dr. Weinberg’s research evaluates immune restoration in antiretroviral therapy.  She has established virologic correlates of immune reconstitution in children and adults, and identified immune correlates of protection against cytomegalovirus (CMV) infection in HIV-infected patients. She has developed several lines of investigation of CMV-specific immunity in transplant patients, including the following: impact of CMV infection on graft rejection-immune restoration in bone marrow transplant recipients and immune correlates of protection against CMV infections; use of dendritic cells for establishment of CMV-specific immunity in stem cell and cord blood transplant recipients.  Dr. Weinberg recently described persistent inhibition of cellular immunity to CMV in HIV-infected patients, but not in healthy individuals.  A potential research training project for ADEAR trainees is laboratory studies of the molecular mechanisms of inhibition of cellular immunity in infants exposed to antiretrovirals in utero. 

Email: ADRIANA.WEINBERG@CUANSCHUTZ.EDU

Faculty Website: https://medschool.cuanschutz.edu/pathology/department-of-pathology-about-us/faculty/university-of-colorado-anschutz-medical-campus/adriana-weinberg-ucd2245

Cara Wilson, M.D., Professor of Medicine, Division of Infectious Diseases, and Vice Chair for Faculty Advancement in the Department of Medicine (UC-AMC).  Dr. Wilson is an experienced cellular immunologist who investigates the role of dendritic cells and HIV-specific T cells in the control of HIV replication.  She is Associate Program Director for the Medical Scientist Training Program at the University of Colorado.  Dr. Wilson is an expert in dendritic cell biology and the role of dendritic cells in HIV pathogenesis.  ADEAR trainees can engage in cutting-edge laboratory-based studies of both helper and cytotoxic T-cell responses to HIV, mechanisms of HIV-associated dendritic cell-dependent immunodeficiency, and studies of the mechanisms of induction of HIV specific immune responses with therapeutic HIV vaccines. 

Email: CARA.WILSON@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/3929

Joshua Barocas, MD, Associate Professor of Medicine, Division of Infectious Diseases (UC-AMC). Dr. Barocas leads an interdisciplinary research program that is specifically aimed at the goal of improving health outcomes for patients with infectious diseases including HIV and HCV, substance use disorders, and other vulnerable populations. His research, which uses clinical epidemiology, health economics, simulation modeling, and cost-effectiveness, informs clinical-decision making and health policy to answer clinically- and policy-relevant questions. He is engaged in research using these innovative methods to help understand the impact of and improve upon policies that affect people who use drugs infected with or at high risk for HIV, viral hepatitis, and other infectious diseases. He has specific expertise in simulation modeling and health economics at the intersection of infectious diseases and substance use disorders. Dr. Barocas serves as the Director of the Health Economics and Modeling Core for the Massachusetts HEALing Communities Study, an NIH-funded multi-institutional grant to significantly reduce overdose. He is also Research Affiliate for the NIDA-supported Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH).

Email: JOSHUA.BAROCAS@CUANSCHUTZ.EDU

Faculty Website: https://som.ucdenver.edu/Profiles/Faculty/Profile/35747

Current Trainees

James Curlin, PhD

Project Title:

A Dual-Purpose hu-Mouse Model for Simultaneous Testing of anti-HIV and anti-SIV drugs.

Publications:

1. Schmitt K, Curlin J, Remling-Mulder L, Moriarty R, Goff K, O'Connor S, Stenglein M, Marx P, Akkina R. Mimicking SIV chimpanzee viral evolution toward HIV-1 during cross-species transmission. J Med Primatol. 2020 Oct;49(5):284-287. doi: 10.1111/jmp.12485. Epub 2020 Aug 17. PMID: 33460210; PMCID: PMC8177655.
2. Curlin J, Schmitt K, Remling-Mulder L, Moriarty R, Goff K, O'Connor S, Stenglein M, Marx P, Akkina R. Evolution of SIVsm in humanized mice towards HIV-2. J Med Primatol. 2020 Oct;49(5):280-283. doi: 10.1111/jmp.12486. Epub 2020 Aug 10. PMID: 32777101; PMCID: PMC8162839.
3. Curlin J, Schmitt K, Remling-Mulder L, Moriarty R, Stenglein M, O'Connor S, Marx P, Akkina R. SIVcpz cross-species transmission and viral evolution toward HIV-1 in a humanized mouse model. J Med Primatol. 2020 Feb;49(1):40-43. doi: 10.1111/jmp.12440. Epub 2019 Oct 1. PMID: 31576587; PMCID: PMC6942238.
4. Schmitt K, Curlin J, Remling-Mulder L, Moriarty R, Goff K, O'Connor S, Stenglein M, Marx P, Akkina R. Cross-Species Transmission and Evolution of SIV Chimpanzee Progenitor Viruses Toward HIV-1 in Humanized Mice. Front Microbiol. 2020 Aug 11;11:1889. doi: 10.3389/fmicb.2020.01889. PMID: 32849468; PMCID: PMC7432304.
5. Schmitt K, Curlin J, Kumar DM, Remling-Mulder L, Feely S, Stenglein M, O'Connor S, Marx P, Akkina R. SIV progenitor evolution toward HIV: A humanized mouse surrogate model for SIVsm adaptation toward HIV-2. J Med Primatol. 2018 Oct;47(5):298-301. doi: 10.1111/jmp.12380. PMID: 30255956; PMCID: PMC6464631.
6. Schmitt K, Charlins P, Veselinovic M, Kinner-Bibeau L, Hu S, Curlin J, Remling-Mulder L, Olson KE, Aboellail T, Akkina R. Zika viral infection and neutralizing human antibody response in a BLT humanized mouse model. Virology. 2018 Feb;515:235-242. doi: 10.1016/j.virol.2017.12.026. Epub 2018 Jan 6. PMID: 29310105; PMCID: PMC5906046.
7. Schmitt K, Mohan Kumar D, Curlin J, Remling-Mulder L, Stenglein M, O'Connor S, Marx P, Akkina R. Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice. Virology. 2017 Oct;510:175-184. doi: 10.1016/j.virol.2017.07.005. Epub 2017 Jul 24. PMID: 28750321; PMCID: PMC5906053.
8. Pope WH, Bowman CA, Russell DA, Jacobs-Sera D, Asai DJ, Cresawn SG, Jacobs WR, Hendrix RW, Lawrence JG, Hatfull GF; Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science; Phage Hunters Integrating Research and Education; Mycobacterial Genetics Course. Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity. Elife. 2015 Apr 28;4:e06416. doi: 10.7554/eLife.06416. PMID: 25919952; PMCID: PMC4408529.
9. Curlin J. (2015) “The Effect of Serrate Transmembrane Domain Substitution on Notch Signaling”. Bachelor of Science Honors Thesis. Trinity College

Brendan Freitas, PhD

Project Title:

Cryo-EM studies of HIV-1 capsid protein (CA) with small molecule inhibitors and cellular co-factors

Publications:

1. Reynolds ND, Aceves NM, Liu JL, Compton JR, Leary DH, Freitas BT, Pegan SD, Doctor KZ, Wu FY, Hu X, Legler PM. The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease. ACS Infect Dis. 2021 Jun 11;7(6):1483-1502. doi: 10.1021/acsinfecdis.0c00866. Epub 2021 May 21. PMID: 34019767; PMCID: PMC8171221.
2. Baker CA, Bester SM, Kirkpatrick MG, Boeri MV, Kasten S, Freitas BT, Pegan SD, Otto TC., Engineering improved stereoselectivity within Brevundimonas diminuta organophosphorus hydrolase for pesticides (Unclassified Title), classified Journal of Chemical and Biological Defense. 2021. 2: 63-78.
3. Dzimianski JV, Mace SL, Williams IL, Freitas BT, Pegan SD. Flipping the substrate preference of Hazara virus ovarian tumour domain protease through structure-based mutagenesis. Acta Crystallogr D Struct Biol. 2020 Nov 1;76(Pt 11):1114-1123. doi: 10.1107/S2059798320012875. Epub 2020 Oct 16. PMID: 33135682; PMCID: PMC7604911.
4. Freitas BT, Durie IA, Murray J, Longo JE, Miller HC, Crich D, Hogan RJ, Tripp RA, Pegan SD. Characterization and Noncovalent Inhibition of the Deubiquitinase and deISGylase Activity of SARS-CoV-2 Papain-Like Protease. ACS Infect Dis. 2020 Aug 14;6(8):2099-2109. doi: 10.1021/acsinfecdis.0c00168. Epub 2020 Jun 4. PMID: 32428392; PMCID: PMC7274171.
5. Freitas BT, Scholte FEM, Bergeron É, Pegan SD. How ISG15 combats viral infection. Virus Res. 2020 Sep;286:198036. doi: 10.1016/j.virusres.2020.198036. Epub 2020 May 31. PMID: 32492472; PMCID: PMC7483349.
6. Dzimianski JV, Scholte FEM, Williams IL, Langley C, Freitas BT, Spengler JR, Bergeron É, Pegan SD. Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases. PLoS One. 2019 Dec 23;14(12):e0226415. doi: 10.1371/journal.pone.0226415. PMID: 31869347; PMCID: PMC6927636.
7. Scholte FEM, Spengler JR, Welch SR, Harmon JR, Coleman-McCray JD, Freitas BT, Kainulainen MH, Pegan SD, Nichol ST, Bergeron É, Spiropoulou CF. Single-dose replicon particle vaccine provides complete protection against Crimean-Congo hemorrhagic fever virus in mice. Emerg Microbes Infect. 2019;8(1):575-578. doi: 10.1080/22221751.2019.1601030. PMID: 30947619; PMCID: PMC6455139.
8. Sheng J, Gou W, Ash C, Freitas B, Paoletti M, Feng Xueyang., Data-Driven Prediction of CRISPRBased Transcription Regulation for Programmable Control of Metabolic Flux. arXiv, 2017 Apr 10; 1704.03027

Past Trainees

Stephanie Bester, PhD

Project Title:

The structural platform for understanding drug-resistance to HIV capsid inhibitor,

Lenacapavir, and developing second generation inhibitors.

Publications:

1. McGuire JR, Bester SM, Guelta MA, Cheung J, Langley C, Winemiller MD, Bae SY, Funk V, Myslinski JM, Pegan SD, Height JJ. Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6. Chem Res Toxicol. 2021 Mar 15;34(3):804-816. doi: 10.1021/acs.chemrestox.0c00406. Epub 2021 Feb 4. PMID: 33538594.
2. Bester SM, Wei G, Zhao H, Adu-Ampratwum D, Iqbal N, Courouble VV, Francis AC, Annamalai AS, Singh PK, Shkriabai N, Van Blerkom P, Morrison J, Poeschla EM, Engelman AN, Melikyan GB, Griffin PR, Fuchs JR, Asturias FJ, Kvaratskhelia M. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020 Oct 16;370(6514):360-364. doi: 10.1126/science.abb4808. PMID: 33060363; PMCID: PMC7831379.
3. Bester SM., Adipietro KA., Funk VL., Myslinkski J., Keul ND., Cheung J., Wilder PT., Wood ZA.,Weber DJ., Height JJ., Pegan SD., The structural and biochemical impact of monomerizing human acetylcholinesterase. Protein Science. 2019, 28 (6), 1106-1114. [Featured Article/Cover]
4. Hsu F., Bae SY., McGuire J., Anderson DR., Bester SM., Height JJ., Pegan SD., Walz AJ., Revisiting the synthesis and molecular properties of broad-spectrum nerve agent reactivator HLö-7 dimethanesulfonate. ACS Med. Chem. Lett. 2019, 10 (5) 761-766.
5. Bester SM., Guelta MA., Cheung J., Winemiller MD., Bae SY., Myslinski J., Pegan SD., Height JJ., Structural insights of stereospecific inhibition of human acetylcholinesterase by VX and subsequent reactivation by HI-6. Chem Res Toxicol 2018, 31 (12), 1405–1417. PMID: 30462502. [Featured Article/Cover]
6. Bester SM and Daczkowski C., Faaberg K., Pegan SD., Insights into PRRSV viral ovarian tumor domain protease specificity for ubiquitin and interferon-stimulated gene product 15, ACS Infect Dis 2018, 4 (9), 1316-1326. PMID: 29856201

Awards:

Ward Smith Award for Excellence in Macromolecular Crystallographic Research