HIV/AIDS | Montefiore Einstein

Barry S. Zingman, M.D., has been the Medical Director of the AIDS Center at Montefiore since 2003 following his service as Medical Director of the AIDS Center's Center for Positive Living/Infectious Diseases (CPL/ID) Clinic for five years.
Dr. Zingman directs the largest multidisciplinary and multispecialty adult HIV/AIDS treatment and prevention program in New York State. His program’s clinical sites include (1) the Center for Positive Living/I.D. Clinic, for HIV, Hepatitis C, and general Infectious Diseases care; (2) The Oval Center at Montefiore, which provides screening and treatment for sexually transmitted infections, HIV pre- and post-exposure prophylaxis programs, and Hepatitis C care; and (3) other inpatient and outpatient sites at the Moses Division of Montefiore Medical Center. He has been Principal Investigator or Medical Director on over 75 HIV/AIDS-related research protocols and grants. These currently include grants from HRSA, the New York State Department of Health's AIDS Institute, NIH, and industry for multidisciplinary HIV primary care and testing; HIV retention, adherence and viral suppression; studies of broadly-neutralizing therapeutic HIV antibodies; new HIV viral load assays; response to pneumococcal vaccine in HIV+ and HIV- individuals; and studies of other new antiretroviral agents.
Dr. Zingman directs an HIV research team consisting of 6 study coordinators that enrolls over 200 patients per year into research protocols.
Dr. Zingman is Professor of Clinical Medicine at Albert Einstein College of Medicine. He is formerly Chair of the AIDS Institute's Medical Care Criteria Committee (the principal body setting HIV care guidelines in NYS); former Vice-Chair of the NYS AIDS Institute's Quality of Care Advisory Committee; and Chair or Member on numerous other state and national HIV quality and standard of care subcommittees. He is a practicing infectious diseases subspecialist and maintains an active patient panel in the CPL/ID Clinic and the Department of Medicine Faculty Practice.

Specialties

Infectious Diseases

Expert Tags

HIV/AIDS

COVID-19

Areas of Expertise

HIV/AIDS

STDs

Sexual education

PrEP

Expert Summary

Dr. Zingman directs the largest multidisciplinary and multispecialty adult HIV/AIDS treatment and prevention program in New York State. His program’s clinical sites include (1) the Center for Positive Living/I.D. Clinic, for HIV, Hepatitis C, and general Infectious Diseases care; (2) The Oval Center at Montefiore, which provides screening and treatment for sexually transmitted infections, HIV pre- and post-exposure prophylaxis programs and Hepatitis C care; and (3) other inpatient and outpatient sites at the Moses Division of Montefiore Medical Center. He has been Principal Investigator or Medical Director on over 75 HIV/AIDS-related research protocols and grants. These currently include grants from HRSA, the New York State Department of Health's AIDS Institute, NIH, and industry for multidisciplinary HIV primary care and testing; HIV retention, adherence and viral suppression; studies of broadly-neutralizing therapeutic HIV antibodies; new HIV viral load assays; response to pneumococcal vaccine in HIV+ and HIV- individuals; and studies of other new antiretroviral agents.

Research Profile

https://einsteinmed.edu/faculty/2288/Barry-Zingman

Clinical Profile

https://montefioreeinstein.org/profiles/1699850461/barry-s-zingman

CHAM Provider

Off

Professional Title

M.D.

Elsevier Profile

https://einstein.pure.elsevier.com/en/persons/60754344-4ce8-45d1-b1d2-c89b024b6…

EMR ID

3691

Biography

Barry S. Zingman, MD, is Medical Director, AIDS Center and Clinical Director, Infectious Diseases at Montefiore Einstein, and Professor, Medicine at our Albert Einstein College of Medicine. Dr. Zingman cares for people with a wide range of infectious disease conditions including HIV care, HIV prevention (PrEP; PEP), sexually transmitted infections, COVID, MPOX (monkeypox), other viral infections, diabetic foot infections, bone infections, heart and lung infections, post-surgical infections, tuberculosis and many others.After completing his Bachelor of Arts in biochemistry at Brandeis University in 1981, Dr. Zingman attended New York University School of Medicine, earning his Doctor of Medicine in 1985. He completed his internship and residency in internal medicine at Boston City Hospital in 1988. Dr. Zingman continued his training at Boston University School of Medicine, completing clinical and research fellowships in infectious diseases in 1991.Dr. Zingman’s research focuses on new treatments, vaccines, and other preventive strategies for infectious diseases including HIV, sexually transmitted infections, other viral infections, E coli urinary tract infections and others. He has shared his work through peer-reviewed journals, articles, case reports, book chapters, abstracts, and other media as well as presentations, invited lectures and webinars.Dr. Zingman is board certified in Infectious Diseases and Internal Medicine. He is a member of the Infectious Disease Society of America (IDSA) and the HIV Medicine Association of IDSA. In 2017, he was inducted into the Leo M. Davidoff Society for distinguished, caring and committed teaching of medical students.

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Harris Goldstein

Read more about Harris Goldstein

Harris Goldstein

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Provider

Faculty

Expert

First Name

Harris

Last Name

Goldstein

NPI

1790861060

Faculty ID

4281

CMO Specialties

Allergy & Immunology

Cancer

Employment Status

Full Time

Patient Type

Pediatric

Department

einstein-dept-pediatrics

einstein-dept-microbiology-immunology

Gender

Male

Phone

718-430-3385

Titles

Type

Academic

Department

Department of Pediatrics

Department Link

Rank

Professor

Division

Pediatric Allergy & Immunology

Type

Academic

Department

Department of Microbiology & Immunology

Department Link

Rank

Professor

Tags

me-patientcare-cancer-research-stem-cell-cancer-biology

Type

Administrative

Title

Director, Einstein-Rockefeller-CUNY Center for AIDS Research

Locations

Is Primary

Type

Clinical

Location (Address, State, City, Zip)

Not used, will be deleted

Coordinates

POINT (-73.87885 40.88037)

Address Line 1

3415 Bainbridge Avenue

City

Bronx

State

Zip

10467-2403

Location Title

The Children's Hospital at Montefiore

Is Primary

Off

Type

Academic

Location (Address, State, City, Zip)

Not used, will be deleted

Coordinates

POINT (-73.8459022 40.8504961)

Building

Belfer Building

Room

307

Address Line 1

Albert Einstein College of Medicine

Address Line 2

Jack and Pearl Resnick Campus

Address Line 3

1300 Morris Park Avenue

City

Bronx

State

Zip

10461

Location Title

Albert Einstein College of Medicine

Education and Trainings

Education Type Label

Medical Education

Education Institution

Albert Einstein College of Medicine

Education Type Label

Fellowship

Education Institution

National Institutes of Health

Education Type Label

Residency

Education Institution

Jacobi Medical Center

Professional Interests

Weaponizing the Immune System to Cure HIV Infection and Cancer 

Developing next generation CAR-T cell treatments to cure HIV and cancer. Our laboratory is utilizing novel molecular, cellular and biochemical approaches to weaponize the immune system by using an artificial immunity (AI) strategy to boost immune response to treat infectious diseases and cancer.  One strategy we are utilizing is to develop novel CAR-T cells for infusion into people living with HIV (PLWH) which can control HIV infection by efficiently eliminating HIV-infected cells. The development of combinational antiretroviral therapy (ART) which targets different steps in the HIV replication cycle has enabled long-term survival of PLWH. However, despite long-term reduction of HIV to undetectable levels, resurgence of viremia occurs soon after the cessation of ART demonstrating that years of successful suppression of active viral replication did not cure HIV infection. HIV cure was prevented by the presence of HIV reservoirs consisting of latent HIV-infected cells distributed throughout the body, which survive despite standard or intensified ART and can produce infectious virus and reintroduce HIV infection after the cessation of ART.  Nevertheless, HIV has been cured in a few PLWH after transplantation of allogeneic hematopoietic stem cells from donors whose T cells are resistant to HIV infection due to a homozygous mutation in the HIV coreceptor, CCR5. This breakthrough demonstrated that HIV could be cured. However, the high morbidity and mortality associated with bone marrow transplantation limits the routine application of this approach and provides a strong rationale for pursuing alternative strategies for providing ART-free HIV remission by leveraging observations that potent HIV-specific immune responses could provide sustained ART-free remission in PLWH.
The capacity of chimeric antigen receptor (CAR)-T cells engineered to target malignant cells to induce remission and cure in cancer patients made this an attractive approach to provide PLWH with a potent HIV-specific immune response.   Our lab has collaborated with the Caring Cross group to develop, optimize and validate the duo-CAR architecture which co-express two independent CARs (duoCAR-T cells), each recognizing a different gp120 epitope and linked to a different costimulatory signaling domain. We demonstrated that this architecture which targets two highly conserved gp120 epitopes, the CD4 binding site for the HIV gp120 envelope and the HIV co-receptor binding region, enables duoCAR-T cells to be extremely resistant to HIV infection and markedly inhibit in vivo HIV infection by a broad range of variants, which should deter HIV immune escape. After validating the in vitro efficacy of these duoCAR-T cells in tissue culture, we used a humanized mouse model we developed that supports HIV infection to demonstrate the in vivo ability of the duoCAR-T cells to control HIV infection. This data was crucial for supporting the approval of this treatment by the FDA for advancement into clinical trials. The duoCAR-T-cell therapy is currently being evaluated in an ongoing phase I/IIa clinical trial with PLWH (NCT04648046). We are currently developing the next generation of duoCAR-T cells which display increased potency and persistence. In addition, we are developing a new generation of CAR-T cells that we engineered by transduction with antibody-encoding lentiviral gene vectors (LV) enabling T cells which confer them with the ability to produce broadly neutralizing antibodies capable of potently suppressing HIV infection. These CAR-T-B cells can deliver a one-two punch to control HIV infection by not only killing cells already infected with HIV, but also preventing the further spread of infection.
Developing immunobiologics which deliver antigen-specific and co-stimulatory signals to focally activate HIV- and cancer-specific CTLs. Another strategy we are using to weaponize the immune system is a modular biologic platform termed Immuno-STAT (IST), that selectively expands antigen-specific T cells by delivering antigen-specific TCR and co-stimulatory signals through HLA-A2 MHC molecules covalently-tethered to pathogen-derived peptides (pMHC) and linked CD28- or 4-1BB-specific ligands, respectively. These biologics were developed by the Almo lab and immunologically and functionally validated by our lab as an immunotherapeutic for the in vivo expansion of antigen-specific CTL to eliminate virally infected or cancerous cells. The immune response of naïve CD8+ T cells is initiated by three coordinated signals delivered by antigen-presenting cells: Signal 1 delivered by engagement between antigen-specific TCR and its cognate peptide-MHC complex (pMHC); Signal 2 provided by co-stimulatory receptors, such as CD28 and 4-1BB, through interactions with the B7 and 4-1BBL ligands, respectively; and Signal 3 supplied by cytokines, such as IL-7, IL-21, IL-2, or IL-15, which modulate cellular proliferation and differentiation. We demonstrated that ISTs carrying a pMHC alone, a pMHC linked to a CD28 agonist, or pMHC linked to a 4-1BB agonist were all able to induce activation and selective expansion of cytotoxic virus-specific memory CD8+ T cells in vitro and to potently suppressed in vitro and in vivo HIV and CMV infection.
             In addition to using these IST as an immunotherapeutic, we are also using them to delineate the minimum signals required to activate and expand antigen-specific memory CD8+ T cells because they can specifically deliver a T cell receptor (TCR) signal alone or paired with a defined co-stimulatory signal to naïve and memory antigen-specific CD8+ T cells. Using a reductionist approach that provides defined TCR and co-stimulatory signaling, we demonstrated that different IST could engage TCR alone or in combination with either CD28 or 4-1BB costimulatory to initiate distinct transcriptional programs in memory CMV-specific CD8+ T cells. As compared to activation by TCR signaling alone, the combination of TCR and CD28 or 4-1BB co-stimulatory signals significantly altered the transcriptome and drove expression of genes related to growth and survival. Nevertheless, TCR signaling alone was sufficient for robust recall activation and expansion of functional cytomegalovirus CMV-specific and HIV-specific memory CD8+ T cells. This response contrasts with naïve CD8+ T cells, which required CD28 co-stimulation in addition to TCR stimulation for antigen-specific activation. These results have important implications for antigen-specific immunotherapy by indicating that biologics that deliver TCR signals alone may be sufficient for immunotherapeutic strategies designed to expand memory CD8+ T cells to eliminate cancerous or infected cells. However, strategies that aim to stimulate naïve T cell responses would require the codelivery of TCR and CD28 signals.
             We leveraged these findings to applying the IST for developing a new strategy for expanding antigen-specific CD8+ T cells to enable them to be used for adoptive cell transfer (ACT), a promising and rapidly developing immunotherapeutic approach to treat cancer which holds considerable potential as an therapeutic strategy to reconstitute the anti-viral immunity in immune-compromised patients to prevent their development of life-threatening viral infections. We demonstrated that the capacity of this IST platform to deliver TCR and CD28 signals to activate and generate large numbers of highly functional cytotoxic CD8+ T cells from the naïve repertoire specific for the melanoma-associated MART-1 antigen and the HIV-associated SL9 antigen. In contrast to naïve MART-1-specific CD8+ T cells which could be activated by both MART-1-peptide loaded dendritic cells and MART-1-specific IST, naïve SL-9-specific CD8+ T cells could be activated by SL9-specific IST but not by SL9-peptide loaded dendritic cells. This innovative approach has the potential to streamline the expansion of de novo antigen-specific T cells, overcoming the logistical hurdles limiting the wider use of ACT and enhancing its effectiveness as a therapeutic strategy for both cancer and HIV.

Research Areas

HIV therapeutics; HIV Cure; CAR-T cells; TCR structure-function analysis; weaponizing the immune system; molecular and protein engineering of anti-HIV and cancer T cell-based immunotherapeutics; genetic programming of specific TCR and Ig therapeutic immun

Specialties

Infectious Diseases

Expert Tags

HIV/AIDS

Areas of Expertise

Microbiology & Immunology

Expert Summary

Dr. Goldstein’s NIH-funded research centers on developing agents to amplify the capacity of the immune system to control HIV infection and achieve a functional cure for the disease. In seeking to “weaponize” the immune system to cure HIV, his lab uses molecular, cellular, and biochemical approaches, including CAR-T cells and the novel treatment strategy developed by Dr. Almo at Einstein for selective T cell amplification called synTac (synthetic T-cell activation). 
Dr. Goldstein also studies the effects of HIV on the brain and central nervous system and the role of illicit drug use in accelerating HIV infection and causing neurological dysfunction. He is using mouse models developed in his lab to evaluate HIV vaccine candidates and other therapeutics. 
As director of the NIH-funded Einstein-Rockefeller-CUNY Center for AIDS Research, Dr. Goldstein coordinates collaborations by more than 150 investigators from the three institutions. They are working to prevent HIV, to improve health outcomes for people living with HIV, and to find a cure for the HIV infection. In his role as associate dean of scientific resources at Einstein, he assesses new technologies for Einstein’s labs and oversees the work of over 40 shared scientific facilities.

Research Profile

https://einsteinmed.edu/faculty/4281/Harris-Goldstein

Clinical Profile

https://montefioreeinstein.org/profiles/1790861060/harris-goldstein

CHAM Provider

Professional Title

M.D.

Research Focus

HIV pathogenesis; TCR structure-function analysis; genetic programming of specific protective immune responses; genetic manipulation of transplanted beta cells to resist rejection.

Elsevier Profile

https://einstein.pure.elsevier.com/en/persons/4e1f9355-078e-4eae-9dc9-19f420875…

Selected Publications

Graduate student and MSTP student authors are indicated by underlining
Mi T, Soerens AG, Alli S, Kang TG, Vasandan AB, Wang Z, Vezys V, Kimura S, Iacobucci I, Baylin SB, Jones PA, Hiner C, Mueller A, Goldstein H, Mullighan CG, Zebley CC, Masopust D, Youngblood B. Conserved epigenetic hallmarks of T cell aging during immunity and malignancy. Nature Aging. 2024 Jun 12. doi: 10.1038/s43587-024-00649-5. Epub ahead of print. PMID: 38867059.
Su H, Mueller A, Goldstein H. Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission. Curr Opin HIV AIDS. 2024 19:169-178. doi: 10.1097/COH.0000000000000858. Epub 2024 May 1. PMID: 38695148.
Su H, Anthony-Gonda K, Orentas RJ, Dropulić B, Goldstein H. Generation of Anti-HIV CAR-T Cells for Preclinical Research. Methods Mol Biol. 2024;2807:287-298. doi: 10.1007/978-1-0716-3862-0_20. PMID: 38743236.
Shahid A, MacLennan S, Jones BR, Sudderuddin H, Dang Z, Cobarrubias K, Duncan MC, Kinloch NN, Dapp MJ, Archin NM, Fischl MA, Ofotokun I, Adimora A, Gange S, Aouizerat B, Kuniholm MH, Kassaye S, Mullins JI, Goldstein H, Joy JB, Anastos K, Brumme ZL; MACS/WIHS combined cohort study (MWCSS). The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time. J Virology 2024 Jan 12:e0165523. doi: 10.1128/jvi.01655-23. PMID: 38214547.
Anthony-Gonda K, Ray A, Su H, Wang Y, Xiong Y, Lee D, Block A, Chilunda V, Weiselberg J, Zemelko L, Wang YY, Kleinsorge-Block S, Reese JS, de Lima M, Ochsenbauer C, Kappes JC, Dimitrov DS, Orentas R, Deeks SG, Rutishauser RL, Berman JW, Goldstein H, Dropulić B. In vivo killing of primary HIV-infected cells by peripheral-injected early memory-enriched anti-HIV duoCAR T cells. JCI Insight. 2022 Nov 8;7(21):e161698. doi: 10.1172/jci.insight.161698. PMID: 36345941; PMCID: PMC9675454.
Pathela P, Qasmieh S, Gandhi M, Rozen E, Okochi H, Goldstein H, Herold BC, Jamison K, Schillinger JA, Nash D. Brief Report: Use of Remnant Specimens to Assess Use of HIV PrEP Among Populations With Risk of HIV Infection: A Novel Approach. J Acquir Immune Defic Syndr. 2022 Aug 1;90(4):382-387. doi: 10.1097/QAI.0000000000002992. PMID: 35357337; PMCID: PMC9246871.
Qasmieh S, Nash D, Gandhi M, Rozen E, Okochi H, Goldstein H, Herold BC, Jamison K, Pathela P. Self-Reported Use of HIV Preexposure Prophylaxis Is Highly Accurate Among Sexual Health Clinic Patients in New York City. Sex Transm Dis. 2022 Nov 1;49(11):790-793. doi: 10.1097/OLQ.0000000000001622. Epub 2022 Mar 10. PMID: 35312670; PMCID: PMC9463403.
Li M, Garforth SJ, O'Connor KE, Su H, Lee DM, Celikgil A, Chaparro RJ, Seidel RD, Jones RB, Arav-Boger R, Almo SC, Goldstein H. T cell receptor-targeted immunotherapeutics drive selective in vivo HIV- and CMV-specific T cell expansion in humanized mice. J Clin Invest. 2021;131:e141051. doi: 10.1172/JCI141051. PMID: 34673568; PMCID: PMC8631598.
Kinloch NN,  Ren Y, Conce AWD, Dong W, Khadka P, Huang SH, Mota TM, Wilson A, Shahid A, Kirkby D, Harris M, Kovacs C, Benko E, Ostrowski MA, Del Rio Estrada PM, Wimpelberg A, Cannon C, Hardy WD, MacLaren L, Goldstein H, Brumme CJ, Lee GQ, Lynch RM, Brumme ZL, Jones RB. HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA). Nature Commun 2021;12:165. doi: 10.1038/s41467-020-20442-3. PubMed PMID: 33420062 PMCID: PMC7794580
Powell AB,  Ren Y, Korom M, Saunders D, Hanley  PJ, Goldstein H, Nixon DF, Bollard CM, Lynch RM, Jones  RB, Cruz CR. Engineered Antigen-Specific T Cells Secreting Broadly Neutralizing Antibodies: Combining Innate and Adaptive Immune Response against HIV. Mol Ther Methods Clin Dev 2020;19:78-88. doi: 10.1016/j.omtm.2020.08.015. PubMed PMID: 33005704 PMCID: PMC7508916.
Anthony-Gonda K, Bardhi A*, Ray A*, Flerin N, Li M, Chen W, Ochsenbauer C, Kappes JC, Krueger W, Worden A, Schneider D, Zhu Z, Orentas R, Dimitrov D, Goldstein H, Dropulić B. Multi-specific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells. Science Transl Med. 2019:11: pii: eaav5685. doi: 10.1126/scitranslmed.aav5685. PubMed PMID: 31391322.
Flerin NC, Bardhi A*, Zheng JH, Korom M, Folkvord J, Kovacs C, Benko E, Truong R, Mota T, Connick E, Jones RB, Lynch RM, Goldstein H. Establishment of A Novel Humanized Mouse Model to Investigate In Vivo Activation and Depletion of Patient-Derived HIV Latent Reservoirs. J Virology 2019:93: pii: e02051-18. doi: 10.1128/JVI.02051-18. PubMed PMID: 30626677. PMCID: PMC6401459.
Wu Y, Xue J, Wang C, Li W, Wang L, Chen W, Prabakaran P, Kong D, Jin Y, Hu D, Wang Y, Lei C, Yu D, Tu C, Bardhi A, Sidorov I, Ma L, Goldstein H, Qin C, Lu L, Jiang S, Dimitrov DS, Ying T. Rapid Elimination of Broadly Neutralizing Antibodies Correlates with Treatment Failure in the Acute Phase of Simian-Human Immunodeficiency Virus Infection. J Virology 2019;93(20). doi: 10.1128/jvi.01077-19. PubMed PMID: 31375583; PMCID: PMC6798097.

EMR ID

3294

Biography

Harris Goldstein, MD, is an attending physician at the Children’s Hospital at Montefiore Einstein and Senior Associate Dean and Professor, Pediatrics and Microbiology & Immunology at our Albert Einstein College of Medicine, the Charles Michael Chair in Autoimmune Diseases and Director of the Einstein-Rockefeller-CUNY Center for AIDS Research. Dr. Goldstein’s clinical and research focus centers on developing and evaluating CAR-T cells and immunobiologics that deliver antigen-specific and co-stimulatory signals to focally activate specific cytotoxic T cells to treat and potentially cure HIV and cancer.After earning his Doctor of Medicine at the Albert Einstein College of Medicine in 1980, Dr. Goldstein completed his pediatrics residency at Bronx Municipal Hospital Medical Center (Jacobi Hospital) in 1983. He then trained in Allergy and Immunology at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health in the Fauci Laboratory of Immunoregulation as a Medical Staff Fellow (1983-1986) and then Senior Staff Fellow (1986-1987).Dr. Goldstein’s research utilizes novel molecular, cellular and biochemical approaches, including novel CAR T cells to weaponize the immune system by using an artificial immunity (AI) strategy to boost immune response to treat infectious diseases and cancer. He has been principal investigator and co-investigator for over two dozen NIH-funded research projects and has given many invited national and international talks and lectures. Dr. Goldstein has shared his work through peer-reviewed journals, book chapters and abstracts published in a number of scientific journals, including Lancet, Journal of Experimental Medicine, Journal of Clinical Investigation, Proceedings of the National Academy of Sciences, and Science Translational Medicine, among others. He also holds three United States patents.Dr. Goldstein is board certified by the American Board of Pediatrics and the American Board of Allergy and Immunology. Dr. Goldstein has received multiple awards for teaching including the Samuel M. Rosen Outstanding Teacher Award for Instruction in the Pre-Clinical Curriculum, the Harry Eagle Award for Outstanding Basic Science Teaching and the Einstein Lifetime Achievement Award for Excellence in Teaching and induction into the Leo M. Davidoff Society for Excellence in Teaching and the Alpha Omega Alpha Honor Medical Society.

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