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Howard E. Gendelman

Summary

Howard E. Gendelman (born March 18, 1954) is an American physician-scientist whose research intersects the disciplines of neuroimmunology, pharmacology, and infectious diseases. Gendelman was born in Philadelphia, Pennsylvania. His research is focused on harnessing immune responses for therapeutic gain in HIV/AIDS and Neurodegenerative disease.[1] He is the Margaret R. Larson Professor of infectious diseases and internal medicine at the University of Nebraska Medical Center (UNMC) in Omaha.[2]

Howard E. Gendelman, M.D.
BornMarch 18, 1954
Philadelphia, Pennsylvania, USA
NationalityAmerican
Alma materMuhlenberg College
Pennsylvania State University College of Medicine
Known forHIV research, Parkinson's research, neuroimmune-pharmacology
AwardsStartup of the Year 2022 UNeMed; Nebraska Coalition for Lifesaving Cures' 2022 Life Saver Award; 2018 Jewish Federation of Omaha Humanitarian of the Year Award; 2017 Society on NeuroImmune Pharmacology Lifetime Achievement Award; International Society for NeuroVirology's 2016 Pioneer in NeuroVirology; 2000 J. William Fulbright Research Scholar; and others
Scientific career
FieldsVirology, neuroimmunology, neuroscience, pharmacology, therapeutics
InstitutionsCurrent: University of Nebraska Medical Center
Previous: Henry M. Jackson Foundation for the Advancement in Military Medicine
Walter Reed Army Institute of Research
Uniformed Services University of the Health Sciences Center
Johns Hopkins University
Albert Einstein College of Medicine
Websitehttps://www.unmc.edu/pharmacology/faculty/primary-faculty/gendelman/

He is married with three children and seven grandchildren.[3]

Early life and education edit

Gendelman graduated with a bachelor's degree in Natural Sciences and Russian Studies from Muhlenberg College (1971-1975).[3] He completed his doctorate of medicine at the Pennsylvania State University-Hershey Medical Center (1975-1979).[3] He then completed a residency in Internal medicine at Montefiore Hospital, Albert Einstein College of Medicine (1979-1982), and he was a Clinical and Research Fellow in Neurology and Infectious Diseases at the Johns Hopkins University Medical Center (1982-1985).[3]

Career edit

Gendelman worked at the National Institute of Allergy and Infectious Diseases during the height of the HIV/AIDS Pandemic.[4] Gendelman also occupied senior faculty and research positions at the Johns Hopkins Medical Institutions, the Uniformed Services University of the Health Sciences Center, the Walter Reed Army Institute of Research, and the Henry M. Jackson Foundation for the Advancement in Military Medicine before joining the faculty of UNMC in March 1993. He retired from the US Army with the rank of Lieutenant Colonel. He established the Center for Neurovirology and Neurodegenerative Disorders at UNMC in 1997,[5] which evolved into UNMC's current Department of Pharmacology and Experimental Neuroscience in 2004.[6] In 2000, he was awarded a Fulbright to do research at the Weizmann Institute of Science in Rehovot, Israel [7][8]

Research edit

Mononuclear phagocytes and neurodegenerative disease edit

Gendelman's research explores the role of mononuclear phagocytes (monocytes, macrophages, microglia, and dendritic cells) as viral reservoirs, perpetrators of disease, and depots for nanoformulated drug delivery. His work was foundational to building a field of investigation focused on lentiviral pathogenesis, diagnostics, and therapeutics. These advancements in immune transformation have led to new and effective management of neurodegenerative disease progression. Gendelman and his research team were among the first to develop laboratory assays for establishing viral tropism for mononuclear phagocytes, and they were the first to demonstrate that infected and immune activated mononuclear phagocytes release viral and cellular toxins that damage the nervous system.[9][10][11]

HIV research contributions edit

Gendelman's group was among the first to reverse HIV-dementia in an infected person using combination antiretroviral therapy (cART), and they developed scores of rodent models to mimic HIV/AIDS end-organ disease.[12][13][14] He coined the term long-acting slow effective release ART (LASER ART). These works led to polymer discovery, targeted drug delivery to viral reservoirs, and reduction of residual virus in lymphoid organs. His Nebraska-based research group, along with a team at Temple University, was also the first to combine HIV reservoir-targeted LASER ART and CRISPR-Cas9 to eliminate chronic viral infection from infected animals.[15] This curative approach (published in Nature Communications, 2019) received considerable attention in establishing a novel translational pathway for HIV eradication.[16][17][18] This work followed the first ultra-long acting nanocrystal prodrug and the world's first HIV vaccine mimetic[19][20] (in Nature Materials, 2020). His work with cell-based drug delivery born out of nanoparticle-mononuclear phagocyte interactions has inspired broad pharmaceutical interest; in turn, Gendelman led the establishment of the Nebraska Nanomedicine Production Plant,[21] a biotechnology good manufacturing practices (cGMP) initiative, to position research for clinical translation in the development of long acting nanoformulated ART at UNMC. He also co-founded Exavir Therapeutics, Inc.,[22] a biotechnology company developing therapies towards and cure for HIV/AIDS.

Parkinson's Disease research contributions edit

Gendelman was the first to pharmacologically transform effector into regulatory T cells to halt the progression of Parkinson's disease.[23][24] Phase II investigation began in early 2021 after successful phase I investigations[25]

Scientific community leadership edit

Gendelman has written or edited 17 books and monographs (including multiple editions of the textbooks The Neurology of AIDS[26] and Neuroimmune Pharmacology[27]). He was the founding Editor-in-Chief of the Journal of Neuroimmune Pharmacology.

Awards and honors edit

Research recognitions edit

  • Startup of the Year 2022 - Exavir Therapeutics[28]
  • Nebraska Coalition for Lifesaving Cures' 2022 Life Saver Award[29][30]
  • Lifetime Achievement Award, Contribution to the Advancement of the Mission of the Society on NeuroImmune Pharmacology, 2017[31]
  • Pioneer in NeuroVirology, International Society for NeuroVirology, 2016[8]
  • Javits Investigator Award, National Institutes of Health, 2000[32]

References edit

  1. ^ Johnson, Amanda McGill (2022-01-28). "2022 Luncheon Honoreers". Nebraska Cures. Retrieved 2022-10-26./
  2. ^ Temple University Health System (2019-07-02). "HIV eliminated from the genomes of living animals". Science Daily=en-US. Retrieved 2022-10-26.
  3. ^ a b c d Utesch, Margie (2018-07-03). "Humanitarian of the Year". The Jewish Community Center of Omaha. Retrieved 2021-12-16.
  4. ^ "Potential new HIV treatment developed at UNMC". KMTV. 2020-04-29. Retrieved 2021-12-16.
  5. ^ "Front Line (2009)" (PDF). University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience. Retrieved 2022-01-25.
  6. ^ "About Us". University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience. Retrieved 2022-01-25.
  7. ^ "UNMC Professor gets Fulbright to study in Israel (2001)". Daily Nebraskan. 21 March 2000. Retrieved 2022-11-04.
  8. ^ a b "The Pioneer in Neurovirology Award". International Society for NeurVirology. 2016. Retrieved 4 November 2022.
  9. ^ Adachi, A; Gendelman, H E; Koenig, S; Folks, T; Willey, R; Rabson, A; Martin, M A (August 1986). "Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone". Journal of Virology. 59 (2): 284–291. doi:10.1128/jvi.59.2.284-291.1986. ISSN 0022-538X. PMC 253077. PMID 3016298. S2CID 12551511.
  10. ^ Koenig, Scott; Gendelman, Howard E.; Orenstein, Jan M.; Dal Canto, Mauro C.; Pezeshkpour, Gholam H.; Yungbluth, Margaret; Janotta, Frank; Aksamit, Allen; Martin, Malcolm A.; Fauci, Anthony S. (1986-09-05). "Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy". Science. 233 (4768): 1089–1093. Bibcode:1986Sci...233.1089K. doi:10.1126/science.3016903. ISSN 0036-8075. PMID 3016903.
  11. ^ Gendelman, H. E.; Narayan, O.; Molineaux, S.; Clements, J. E.; Ghotbi, Z. (October 1985). "Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow". Proceedings of the National Academy of Sciences of the United States of America. 82 (20): 7086–7090. Bibcode:1985PNAS...82.7086G. doi:10.1073/pnas.82.20.7086. ISSN 0027-8424. PMC 391315. PMID 2996004.
  12. ^ Gendelman, Howard E.; Zheng, Jialin; Coulter, Cynthia L.; Ghorpade, Anuja; Che, Myhanh; Thylin, Michael; Rubocki, Ronald; Persidsky, Yuri; Hahn, Francis; Reinhard, Jr., John; Swindells, Susan (October 1998). "Suppression of Inflammatory Neurotoxins by Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus-Associated Dementia". The Journal of Infectious Diseases. 178 (4): 1000–1007. doi:10.1086/515693. ISSN 0022-1899. PMID 9806027. S2CID 42427863.
  13. ^ Spellman, Lisa (2019-08-09). "Science Cafe explores possibility of HIV cure". University of Nebraska Medical Center. Retrieved 2021-12-16.
  14. ^ Gendelman, Howard E. (2012). The neurology of AIDS. Oxford University Press. ISBN 978-0-19-539934-9. OCLC 828615707.
  15. ^ "Scientists say they found a cure for HIV in some mice. Humans could be next". www.washingtonpost.com. Retrieved 2022-11-23.
  16. ^ "In a first, scientists eliminate HIV from an animal's genome". www.cbsnews.com. 3 July 2019. Retrieved 2021-12-17.
  17. ^ Yancey-Bragg, N'dea. "Researchers have eliminated HIV in mice for the first time. Is a cure for humans next?". USA TODAY. Retrieved 2021-12-17.
  18. ^ Dash, Prasanta K.; Kaminski, Rafal; Bella, Ramona; Su, Hang; Mathews, Saumi; Ahooyi, Taha M.; Chen, Chen; Mancuso, Pietro; Sariyer, Rahsan; Ferrante, Pasquale; Donadoni, Martina (December 2019). "Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice". Nature Communications. 10 (1): 2753. Bibcode:2019NatCo..10.2753D. doi:10.1038/s41467-019-10366-y. ISSN 2041-1723. PMC 6606613. PMID 31266936.
  19. ^ Kulkarni, Tanmay A.; Bade, Aditya N.; Sillman, Brady; Shetty, Bhagya Laxmi Dyavar; Wojtkiewicz, Melinda S.; Gautam, Nagsen; Hilaire, James R.; Sravanam, Sruthi; Szlachetka, Adam; Lamberty, Benjamin G.; Morsey, Brenda M. (August 2020). "A year-long extended release nanoformulated cabotegravir prodrug". Nature Materials. 19 (8): 910–920. Bibcode:2020NatMa..19..910K. doi:10.1038/s41563-020-0674-z. ISSN 1476-1122. PMC 7384935. PMID 32341511.
  20. ^ Soriano, Vicente; Barreiro, Pablo; de Mendoza, Carmen (August 2020). "Long-acting antiretroviral therapy". Nature Materials. 19 (8): 826–827. Bibcode:2020NatMa..19..826S. doi:10.1038/s41563-020-0731-7. ISSN 1476-4660. PMID 32704135. S2CID 220721631.
  21. ^ "Nebraska Nanomedicine Production Plant | Pharmacology | University of Nebraska Medical Center". www.unmc.edu. Retrieved 2021-12-16.
  22. ^ "Exavir Therapeutics". exavirtherapeutics.com. 2021-02-14. Retrieved 2021-12-16.
  23. ^ Benner, Eric J.; Mosley, R. Lee; Destache, Chris J.; Lewis, Travis B.; Jackson-Lewis, Vernice; Gorantla, Santhi; Nemachek, Craig; Green, Steven R.; Przedborski, Serge; Gendelman, Howard E. (2004-06-22). "Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease". Proceedings of the National Academy of Sciences of the United States of America. 101 (25): 9435–9440. Bibcode:2004PNAS..101.9435B. doi:10.1073/pnas.0400569101. ISSN 0027-8424. PMC 438994. PMID 15197276.
  24. ^ Gendelman, Howard E.; Zhang, Yuning; Santamaria, Pamela; Olson, Katherine E.; Schutt, Charles R.; Bhatti, Danish; Shetty, Bhagya Laxmi Dyavar; Lu, Yaman; Estes, Katherine A.; Standaert, David G.; Heinrichs-Graham, Elizabeth (2017-03-23). "Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson's disease trial". npj Parkinson's Disease. 3 (1): 10. doi:10.1038/s41531-017-0013-5. ISSN 2373-8057. PMC 5445595. PMID 28649610.
  25. ^ Olson, Katherine E.; Namminga, Krista L.; Lu, Yaman; Schwab, Aaron D.; Thurston, Mackenzie J.; Abdelmoaty, Mai M.; Kumar, Vikas; Wojtkiewicz, Melinda; Obaro, Helen; Santamaria, Pamela; Mosley, R. Lee (2021-05-01). "Safety, tolerability, and immune-biomarker profiling for year-long sargramostim treatment of Parkinson's disease". eBioMedicine. 67: 103380. doi:10.1016/j.ebiom.2021.103380. ISSN 2352-3964. PMC 8138485. PMID 34000620.
  26. ^ Gendelman, Howard E; Grant, Igor; Everall, Ian Paul; Fox, Howard S; Gelbard, Harris A; Lipton, Stuart A; Swindells, Susan, eds. (2012). The Neurology of AIDS. Oxford University Press. doi:10.1093/med/9780195399349.001.0001. ISBN 978-0-19-996519-9.
  27. ^ Ikezu, Tsuneya; Gendelman, Howard E., eds. (2017). Neuroimmune Pharmacology. doi:10.1007/978-3-319-44022-4. ISBN 978-3-319-44020-0.
  28. ^ "Innovation Awards". UNeMed.com. 23 October 2022. Retrieved 23 November 2022.
  29. ^ "2022 Luncheon Honorees". Nebraska Cures. 28 January 2022. Retrieved 28 April 2022.
  30. ^ "Tribute to Dr. Howard Gendelman and Dr. Bonnie Bloch". YouTube. Nebraska Cures. Retrieved 28 April 2022.
  31. ^ "SNIP - Society on NeuroImmune Pharmacology". s-nip.org. Retrieved 2021-12-16.
  32. ^ "$3 Million Grant Recognizes Potential of Research at the UNMC Center for Neurovirology and Neurodegenerative Disorders". University of Nebraska Medical Center. 2001. Retrieved 4 November 2022.

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