Welcome to the Rinaldo Laboratory

The Rinaldo laboratory studies cellular immunologic responses to human immunodeficiency virus (HIV), Kaposi’s sarcoma associated herpesvirus (KSHV or human herpesvirus 8 [HHV-8]), cytomegalovirus (CMV) and SARS-CoV-2, with the overall goal of curing and preventing these infections. The lab focuses on the functions of professional antigen-presenting cells (myeloid dendritic cells, monocytes/macrophages and B lymphocytes) and their interactions with T cells. Newest areas of this research include (a) single cell transcriptomics to assess cell-to-cell transcriptome heterogeneity and cellular differences concealed by standard, bulk RNA sequencing, and (b) CRISPR/Cas9 gene-editing to target HIV-1 genome activity and immunotherapies, including T cell and natural killer cells, professional antigen presenting cells, and immune checkpoints.

Dr. Rinaldo has had continuous research grant funding from the NIH since 1979. He has mentored many graduate students and postdoctoral fellows who have advanced to prestigious positions in academia, industry and government. He is currently Principal Investigator of the NIH U01 Pitt Men’s Study, which is a clinical research site in the MACS-WIHS Combined Cohort Study, Principal Investigator of an NIH R01 grant on immune responses to COVID-19 vaccines in people with HIV (PWH), Director of an Immunology Specialty Laboratory for the NIH AIDS Clinical Trials Group, and Director of the Systems Biology & Biostatistics Core F of the Rustbelt Center for AIDS Research. These projects provide resources and biologic specimens for a broad variety of important research projects.

Contact

Charles R. Rinaldo, PhD
rinaldo@pitt.edu

Tel: 412-624-392

Laboratory:

817 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261

Meet Our Current Lab Members

Top Row, Left to right: Dr. Yue Chen, Mr. Peter Shoucair, Dr. Charles Rinaldo, Ms. Susan McQuiston, Ms. Abigail Gerberick

Bottom Row, Left to right: Ms. Kathy Hartle, Ms. Arlene Bullotta, Ms. Kathy Kulka, Mr. Patrick Mehta, Mr. Daniel Okpaise

Job Opportunities

Persons interested in technical research positions, graduate degree programs, and postdoctoral fellowships, and who are passionate about these areas of viral immunology research, are encouraged to inquire about open positions in the Rinaldo laboratory. For more information, please contact Dr. Rinaldo at: rinaldo@pitt.edu

•••

Charles R. Rinaldo, Ph.D.
3550 Terrace Street
University of Pittsburgh School of Medicine
Scaife Hall 871
Pittsburgh, PA 15213

Email:
rinaldo@pitt.edu

Office phone:
(412) 624-3928

Rinaldo Laboratory Contributions to Science

CMV infection and immunosuppression

Primary CMV infection is detectable in blood neutrophils and can cause a mononucleosis with a profound, self-limiting immunosuppression in immunocompetent adults. This research was an integral factor referenced in the original CDC report on AIDS, June, 1981. CMV remains a major viral cofactor in HIV infection in current approaches to cure HIV infection.

Key publications related to this work

HIV-1 load as a predictor of AIDS

First reports to demonstrate that HIV-1 RNA levels in blood in the first year of infection can predict risk for development of AIDS 10 years later. Viral load testing remains the standard of care in management and prognosis of HIV infection.

Key publications related to this work

Myeloid dendritic cells (DC) are key to activating latent HIV-1 and inducing anti-HIV-1 T cell immunity

First comprehensive report that programmed DC expressing HIV-1 antigens are potent antigen-presenting cells (APC) and maintain strong induction of cytokines in memory CD8+ T cells during untreated PWH and those on antiretroviral drug therapy (ART). DC can prime naïve T cells to HIV-1 in PWH during ART to produce cytokines and kill HIV-1 infected cells. This research also revealed that immune checkpoint PD-1 on CD8 T cells has dual, contradictory roles in anti-HIV-1 T cell immunity, and that DC activate latent HIV-1 (the “kick”) in CD4 T cells and stimulate CTL that kill these infected cells (“the kill”). DC are being used in “kick and kill” clinical trials to control and ultimately cure HIV-1 infection.

Key publications related to this work

T cell control and DC/B cell targeting by HHV-8 (KSHV)

First reports of primary infection with HHV- 8 (KSHV), CD8+ T cell responses to HHV-8, targeting of APC by HHV-8 via DC-SIGN, and HHV-8 targeting of B cell subsets for lytic infection and poly-cytokine responses in relation to increased risk for KS.

Key publications related to this work

HIV-1 trans infection in nonprogressors

Discovery that HIV-1 trans infection mediated by APC is restricted in nonprogressors due to a genetically inherited alteration in APC cholesterol metabolism. Novel genetic basis for the innate ability of the host to blunt HIV-1 disease progression. This opens new approaches for control of HIV-1 infection, and could have broader, non-HIV-1 clinical implications.

Key publications related to this work

Recent Rinaldo Laboratory Alumni

Research highlighted below was led by these former graduate students and postdoctoral fellows in Dr. Rinaldo’s laboratory in the past decade. To ensure the most medically relevant and important research topics and approaches, Dr. Rinaldo combines his expertise and the specialties of his laboratory team with the talents and knowledge of top-grade collaborators in the Division of Infectious Diseases and other Pitt Departments. Key collaborators in mentoring these alumni and their research projects include Xiao-Li Huang, M.D.; Zheng Fan, M.D.; Giovanna Rappocciolo, Ph.D., Paolo Piazza, Ph.D., Phalguni Gupta, Ph.D., Nicolas Sluis-Cremer, Ph.D., Shyamal Peddada, Ph.D., Frank Jenkins, Ph.D., Yue Chen, Ph.D., and Robbie Mailliard, Ph.D.

Lauren Lepone (Brodd), PhD

Current Position:
Health Science Policy Analyst at NIH Office of Science Policy, Washington, DC

Key research in the Rinaldo Laboratory:
Lepone L, Rappocciolo G, Knowlton E, Jais M, Piazza P, Jenkins FJ, Rinaldo CR. Monofunctional and polyfunctional CD8+ T cell responses to human herpesvirus 8 lytic and latency proteins. Clin Vaccine Immunol. 2010 Oct;17(10):1507-16. doi: 10.1128/CVI.00189-10. PMID: 20719985

Emilee Knowlton, PhD

Current Position:
Immunology Sales Specialist at ProImmune, Inc., Pittsburgh PA

Key research in the Rinaldo Laboratory:
Knowlton ER, Rappocciolo G, Piazza P, Lepone LM, Nadgir SV, Bullotta A, Berendam SJ, Li J, Reinhart TA, Jenkins FJ, Rinaldo CR. Human herpesvirus 8 induces polyfunctional B lymphocytes that drive Kaposi’s sarcoma. mBio. 2014 Sep 2;5(5):e01277-14. doi: 10.1128/mBio.01277-14. PMID: 25182322

Nada Melhem, PhD

Current Position:
Associate Professor of Infectious Diseases and Microbiology, Faculty of Health Sciences, Director of the Division of Health Professions, and Chair of the Medical Laboratory Sciences Program at the Faculty of Health Sciences of the American University of Beirut, Lebanon.

Key research in the Rinaldo Laboratory:
Melhem NM, Smith KN, Huang XL, Colleton BA, Jiang W, Mailliard RB, Mullins JI, Rinaldo CR. The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8⁺ T cell responses.
Virology. 2014 Feb;450-451:34-48. doi: 10.1016/j.virol.2013.10.015. PMID: 24503065

Colleen Zaccard, PhD

Current Position:
Research Assistant Professor at Northwestern University – The Feinberg School of Medicine, Chicago IL

Key research in the Rinaldo Laboratory:
Zaccard CR, Watkins SC, Kalinski P, Fecek RJ, Yates AL, Salter RD, Ayyavoo V, Rinaldo CR, Mailliard RB. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity. J Immunol. 2015 Feb 1;194(3):1047-56. doi: 10.4049/jimmunol.1401832. PMID: 25548234

Kellie N. Smith, PhD

Current Position:
Associate Professor of Oncology, Johns Hopkins University School of Medicine, Baltimore MD

Key research in the Rinaldo Laboratory:
Smith KN, Mailliard RB, Piazza PA, Fischer W, Korber BT, Fecek RJ, Ratner D, Gupta P, Mullins JI, Rinaldo CR. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells. mBio. 2016 May 31;7(3):e00473-16. doi: 10.1128/mBio.00473-16. PMID: 27247230

Diana Campbell (DeLucia), PhD

Current Position:
Postdoctoral Research Fellow, Fred Hutchinson Cancer Center, Seattle WA

Key research in the Rinaldo Laboratory:
DeLucia DC, Rinaldo CR, Rappocciolo G. Inefficient HIV-1 trans Infection of CD4+ T Cells by Macrophages from HIV-1 Nonprogressors Is Associated with Altered Membrane Cholesterol and DC-SIGN.
J Virol. 2018 Jun 13;92(13):e00092-18. doi: 10.1128/JVI.00092-18. PMID: 29643243

Jan Kristoff, PhD

Current Position:
Senior Scientist, Merck, Infectious Disease and Vaccines, West Point, PA

Key research in the Rinaldo Laboratory:
Kristoff J, Palma ML, Garcia-Bates TM, Shen C, Sluis-Cremer N, Gupta P, Rinaldo CR, Mailliard RB. Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1. EBioMedicine. 2019 May;43:295-306. doi: 10.1016/j.ebiom.2019.03.077. PMID: 30952614

Tatiana Garcia-Bates, PhD

Current Position:
Senior Scientist II, Cell Therapy R&D,
Dispatch Biotherapeutics, Philadelphia, PA

Key research in the Rinaldo Laboratory:
Garcia-Bates TM, Palma ML, Anderko RR, Hsu DC, Ananworanich J, Korber BT, Gaiha GD, Phanuphak N, Thomas R, Tovanabutra S, Walker BD, Mellors JW, Piazza PA, Kroon E, Riddler SA, Michael NL, Rinaldo CR, Mailliard RB; I4C and RV254 Study Groups. Dendritic cells focus CTL responses toward highly conserved and topologically important HIV-1 epitopes. EBioMedicine. 2021 Jan;63:103175. doi: 10.1016/j.ebiom.2020.103175.
PMID: 33450518

Mariah Cole, MS

Current Position:
Clinical Scientist, Paraxel, Rochester, NY

Key research in the Rinaldo Laboratory:
Chen Y, Lin H, Cole M, Morris A, Martinson J, Mckay H, Mimiaga M, Margolick J, Fitch A, Methe B, Srinivas VR, Peddada S, Rinaldo CR. Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM. Microbiome 2021 Dec 9;9(1):237. doi: 10.1186/s40168-021-01168-w. PMID: 34879869; PMCID: PMC8656045.

Laura Stewart, MPH

Current Position:
Applied Epidemiologist, Allegheny County Health Department, Pittsburgh, PA

Key research in the Rinaldo Laboratory:
Chen, Y., Bullotta A., Martinson, J., Stewart, L., Rinaldo, C. Detection of the virome in the CNS of people with HIV. Ongoing study.

Grace Abror, MPH

Current Position:
Clinical Research Assistant, Pitt Men’s Study, Department of Medicine, University of Pittsburgh, Pittsburgh PA

Key research in the Rinaldo Laboratory:
Gut microbiome mediates the effects of sexual behaviors of men having sex with men on their HIV-1 seroconversion status. Manuscript in preparation.

Division of Infectious Diseases
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