CHEETAH Center for the Structural Biology of HIV Infection, Restriction and Viral Dynamics

CRNA—Center for Structural Biology of HIV RNA

Centers for HIV Structural Biology

The Centers for HIV Structural Biology, established in 2007 by the National Institute of General Medical Sciences (NIGMS), integrate a variety of techniques from structural biology, biochemistry and cell biology to capture in unprecedented detail the three-dimensional structures of HIV proteins and nucleic acids and their interactions with cellular components. This information will help elucidate how the different components interact and reveal new approaches for disrupting those interactions, potentially leading to new targets for HIV therapies and preventive vaccines.

The Center awards were transferred from NIGMS to NIAID in 2019 as a part of the consolidation of AIDS basic research projects in the NIAID Division of AIDS. The program was continued in 2022 with the funding of six new Centers. The Centers include research across the HIV life cycle, aiming, for example, to elucidate the mechanism the HIV envelope protein uses to enter a target cell, the interactions of virus structures with host proteins that either facilitate or antagonize infection, and the way that the HIV RNA genome folds into complex assemblies with other viral components before being packaged into newly formed virions. 

Main Areas of Focus

  • Structural Biology of HIV, molecular complexes, and HIV / host cell complexes including proteins, nucleic acids and pharmacologic inhibitors.
  • Identification of new host cell factors involved in HIV replication and restriction
  • Identification of new targets for anti-HIV drug development and vaccine design

Contact Information

David McDonald, PhD, Basic Sciences Program, Division of AIDS, NIAID

Locations
Funding

RFA-AI-21-030: Centers for HIV Structural Biology (U54)
RFA-AI-22-050: Molecular Dynamics of HIV (R01 Clinical Trial Not Allowed)
NIAID Funding News: Molecular Dynamics of HIV Funding Opportunity 

Events

2025 HIV Structural Biology Virtual Meeting
Monday, June 23 - Tuesday, June 24, 2025
Open to U54 Structure Center Members
Pre-registration required

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Antimicrobial Resistance Threats

P’ng Loke, Ph.D.

Chief, Type 2 Immunity Section

Major Areas of Research

  • Type 2 cytokine (IL-4 and IL-13) activated macrophages during helminth infections
  • Role of microbiota during helminth infections
  • Genetic and environmental contributions towards immune variation between individuals
  • Helminth infections, inflammatory bowel diseases, metabolic syndrome, atherosclerosis, chronic inflammation

Biography

Dr. P’ng Loke completed his Ph.D. research at the University of Edinburgh on IL-4 activated macrophages responding to Brugia malayi filarial parasites in 2001. He then did postdoctoral research on costimulatory molecules at University of California-Berkeley and studied macrophage responses to different parasites at University of California-San Francisco. In 2009, he joined New York University School of Medicine as an assistant professor and was a tenured associate professor before he joined the Laboratory of Parasitic Diseases as a senior investigator in 2020.

Program Description

Our research goal is to understand the heterogeneity of type-2 immune responses during helminth infections. Although we have co-evolved with helminths and most infections are asymptomatic, these parasites can cause pathology in some individuals that either mount a response that is too strong or too weak during infection. An appropriately regulated type-2 response is critical in maintaining the balance between expelling enough parasites and tolerating the remaining parasites without excessive collateral tissue damage, in order to maintain the fitness of the host.

Type-2 immunity induced by helminth infections may be therapeutically beneficial for improving symptoms of inflammatory bowel diseases and metabolic syndrome, but this may also benefit only specific subsets of individuals. The mechanisms underlying the heterogeneity of type-2 responses between individuals still remains poorly understood. We believe that characterizing these mechanisms will enable us to develop strategies to utilize helminth infections as treatment for specific inflammatory conditions (e.g., autoimmune diseases and metabolic conditions) for the right individuals, as well as designing better approaches toward limiting pathology that is caused by helminth infections.

Our basic immunological studies on macrophage biology and our translational research studies on the microbiota are converging toward the goal of understanding factors that regulate variation of type-2 immune responses in humans. Using a combination of mouse models, as well as field and clinical studies, our future plans are to test some of the concepts that we have developed on chromatin remodeling in macrophage responses to type-2 cytokines, as well as helminth-microbiota interactions, in mouse models, field studies and also human challenge infections.

Research Group

Jian-Da Lin, Ph.D., Staff Scientist

Selected Publications

Lee SC, Tang MS, Easton AV, Devlin JC, Chua LL, Cho I, Moy FM, Khang TF, Lim YAL, Loke P. Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures. PLoS Pathog. 2019 Dec 16;15(12):e1008066.

Gundra UM, Girgis NM, Gonzalez M, Ouimet M, Tang MS, Vozhilla N, Fisher EA, Moore KJ, Loke P. Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation. Nature Immunology. 2017 Jun;18(6):642-653.

Ramanan D*, Bowcutt R*, Lee SC, Tang MS, Honda K, Gause WC, Lim YAL, Loke P**, Cadwell K**. Helminth infection promotes colonization resistance via type 2 immunity. Science. 2016 Apr 29;352(6285):608-12. * Equally contributing first authors. ** Equally contributing senior authors.

Gundra UM, Girgis NM, Ruckerl D, Jenkins S, Ward LN, Kurtz ZD, Wiens KE, Tang MS, Basu-Roy U, Mansukhani A, Allen JE, Loke P. Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct. Blood. 2014 May 15;123(20):e110-22.

Broadhurst MJ, Leung JM, Kashyap V, McCune JM, Mahadevan U, McKerrow JH, Loke P. IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient. Sci Transl Med. 2010 Dec 1;2(60):60ra88.

Visit PubMed for a complete publication list.

Section or Unit Name
Type 2 Immunity Section
First Name
P’ng
Last Name
Loke
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Ph.D.
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Program Description

Our research goal is to understand the heterogeneity of type-2 immune responses during helminth infections. Although we have co-evolved with helminths and most infections are asymptomatic, these parasites can cause pathology in some individuals that either mount a response that is too strong or too weak during infection. An appropriately regulated type-2 response is critical in maintaining the balance between expelling enough parasites and tolerating the remaining parasites without excessive collateral tissue damage, in order to maintain the fitness of the host.

Type-2 immunity induced by helminth infections may be therapeutically beneficial for improving symptoms of inflammatory bowel diseases and metabolic syndrome, but this may also benefit only specific subsets of individuals. The mechanisms underlying the heterogeneity of type-2 responses between individuals still remains poorly understood. We believe that characterizing these mechanisms will enable us to develop strategies to utilize helminth infections as treatment for specific inflammatory conditions (e.g., autoimmune diseases and metabolic conditions) for the right individuals, as well as designing better approaches toward limiting pathology that is caused by helminth infections.

Our basic immunological studies on macrophage biology and our translational research studies on the microbiota are converging toward the goal of understanding factors that regulate variation of type-2 immune responses in humans. Using a combination of mouse models, as well as field and clinical studies, our future plans are to test some of the concepts that we have developed on chromatin remodeling in macrophage responses to type-2 cytokines, as well as helminth-microbiota interactions, in mouse models, field studies and also human challenge infections.

Selected Publications

Devlin JC, Axelrad J, Hine AM, Chang S, Sarkar S, Lin JD, Ruggles KV, Hudesman D, Cadwell K, Loke P. Single-Cell Transcriptional Survey of Ileal-Anal Pouch Immune Cells From Ulcerative Colitis Patients. Gastroenterology. 2021 Apr;160(5):1679-1693.

Gause WC, Rothlin C, Loke P. Heterogeneity in the initiation, development and function of type 2 immunity. Nat Rev Immunol. 2020 Oct;20(10):603-614.  

Lin JD, Devlin JC, Yeung F, McCauley C, Leung JM, Chen YH, Cronkite A, Hansen C, Drake-Dunn C, Ruggles KV, Cadwell K, Graham AL, Loke P. Rewilding Nod2 and Atg16l1 Mutant Mice Uncovers Genetic and Environmental Contributions to Microbial Responses and Immune Cell Composition. Cell Host Microbe. 2020 May 13;27(5):830-840.e4.

Lee SC, Tang MS, Easton AV, Devlin JC, Chua LL, Cho I, Moy FM, Khang TF, Lim YAL, Loke P. Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures. PLoS Pathog. 2019 Dec 16;15(12):e1008066.

Gundra UM, Girgis NM, Gonzalez MA, San Tang M, Van Der Zande HJP, Lin JD, Ouimet M, Ma LJ, Poles J, Vozhilla N, Fisher EA, Moore KJ, Loke P. Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation. Nat Immunol. 2017 Jun;18(6):642-653.

Ramanan D, Bowcutt R, Lee SC, Tang MS, Kurtz ZD, Ding Y, Honda K, Gause WC, Blaser MJ, Bonneau RA, Lim YA, Loke P, Cadwell K. Helminth infection promotes colonization resistance via type 2 immunity. Science. 2016 Apr 29;352(6285):608-12.

Visit PubMed for a complete publication list.

Additional Information

Training Program

NIH-Penn Immunology Graduate Partnership Program
https://www.med.upenn.edu/nih-igg-partnership/

Major Areas of Research
  • Type 2 cytokine (IL-4 and IL-13) activated macrophages during helminth infections
  • Role of microbiota during helminth infections
  • Genetic and environmental contributions towards immune variation between individuals
  • Helminth infections, inflammatory bowel diseases, metabolic syndrome, atherosclerosis, chronic inflammation
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CIVICs Locations

Primary contract awardees for the CIVICS Vaccine Centers, Vaccine Manufacturing & Toxicology Core, Clinical Core, and Statistical, Data Management, and Coordination Center.

Collaborative Influenza Vaccine Innovation Centers (CIVICs)

CIVICs is a network of research centers that works together in a coordinated, multidisciplinary effort to develop more durable, broadly protective and longer-lasting influenza vaccines. The CIVICs program includes three Vaccine Centers, one Vaccine Manufacturing and Toxicology Core, two Clinical Cores, and one Statistical, Data Management, and Coordination Center (SDMCC).

Read more about this network: NIAIDCIVICs.org

Main Areas of Focus

The Vaccine Centers focus on designing novel vaccine candidates and delivery platforms with an emphasis on cross-protective vaccine strategies that could be used in healthy adults as well as populations at high risk for the most serious outcomes of influenza, such as children, older adults, and pregnant women. The Vaccine Centers also focus on new ways to study influenza viruses and the human immune response to influenza through computer modeling, animal models and human challenge trials.

The most promising candidate vaccines will advance to clinical trials conducted by the Clinical Cores. The Vaccine Manufacturing and Toxicology Core will work with the Vaccine Centers to develop and manufacture the vaccine candidates for clinical testing. Vaccine candidates will first be evaluated for safety and immunogenicity in small Phase 1 clinical trials conducted among healthy adult participants. Successful vaccine candidates may eventually be advanced to larger Phase 2 clinical trials in healthy adults, or in specific age groups or at-risk populations.

The CIVICs Statistical, Data Management, and Coordination Center (SDMCC) provides assistance in designing statistically sound clinical trials. The SDMCC also performs clinical data analyses, curates pre-clinical data generated by the Vaccine Centers to ensure that results are available across the CIVICs program and deposited in publicly accessible databases, and provides a public portal for communication to the scientific community and general public about CIVICs program goals and accomplishments.

Locations

Primary contract awardees for the CIVICS Vaccine Centers, Vaccine Manufacturing & Toxicology Core, Clinical Core, and Statistical, Data Management, and Coordination Center.

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