Durham Research Center, 8008
985880 Nebraska Medical Center
Omaha, NE 68198-5880
Keywords:HIV, neuroAIDS, long-acting antiretrovirals, nanomedicine, macrophages, neuroregeneration, Parkinson's Disease
In the news
Dr. Gendelman's biographical information
Visit Dr. Gendelman's laboratory
Chemically modified drug out of UNMC could hasten an HIV cure
Julie Anderson, Omaha World-Herald | February 10, 2018
WOWT | February 8, 2018
UNMC building medicine-making a lab
UNMC Today | February 6, 2018
Chemically modified drug shows promise for HIV treatment, elimination
UNMC Today | November 13, 2017
Time out with T. O. - One neuron at a time
The Lancet Neurology | OnLine First, August 11, 2017
T Cells and Parkinson's disease
UNMC Today | June 9, 2017
Dr. Gendelman honored for humanitarian work
The Jewish Press | May 19, 2017
Jewish Federal of Omaha Humanitarian of the Year
Live Well Nebraska, Julie Anderson | March 27, 2017
UNMC researchers reach milestone in effort to slow or halt progression of Parkinson's
UNMC Today | February 1, 2017
Novel pharmaceutic action for HIV/AIDS discovered
Dr. Howard E. Gendelman is the Margaret R. Larson Professor of Internal Medicine and Infectious Diseases, Chairman of the Department of Pharmacology and Experimental Neuroscience, and Director of the Center for Neurodegenerative Disorders at the University of Nebraska Medical Center. Dr. Gendelman is credited in unraveling how functional alterations in brain immunity induce metabolic changes and ultimately lead to neural cell damage for a broad range of infectious, metabolic and neurodegenerative disorders. These discoveries have had broad implications in developmental therapeutics aimed at preventing, slowing or reversing neural maladies. He is also credited for the demonstration that AIDS dementia is a reversible metabolic encephalopathy; a finding realized at the University of Nebraska Medical Center. His work has led to novel immunotherapy and nanomedicine strategies for Parkinson’s and viral diseases being tested in early clinical trials as a result of intense translational investigations.
Dr. Gendelman obtained a Bachelor’s degree in Natural Sciences and Russian Studies with honors from Muhlenberg College and his M.D. from the Pennsylvania State University-Hershey Medical Center where he was the 1999 Distinguished Alumnus. He completed a residency in Internal medicine at Montefiore Hospital, Albert Einstein College of Medicine and was a Clinical and Research Fellow in Neurology and Infectious Diseases at the Johns Hopkins University Medical Center. He occupied senior faculty and research positions at the Johns Hopkins Medical Institutions, the National Institute of Allergy and Infectious Diseases, the Uniformed Services University of the Health Sciences Center, the Walter Reed Army Institute of Research, and the Henry Jackson Foundation for the Advancement in Military Medicine before joining the University of Nebraska Medical Center faculty in March of 1993. He retired from the US Army with the rank of Lieutenant Colonel. Dr. Gendelman has authored over 400 peer-reviewed publications, edited nine books and monographs, holds eight patents, is the Editor-In-Chief and Founder of the Journal of Neuroimmune Pharmacology along with service on numerous editorial boards, national and international scientific review and federal and state committees. He has been an invited lecturer to more than 200 scientific seminars and symposia and the recipient of numerous local, national and international honors. These, include, but are not limited to, the Henry L. Moses Award in Basic Science; the Carter-Wallace Fellow for Distinction in AIDS Research, the David T. Purtilo Distinguished Chair of Pathology and Microbiology, the UNMC Scientist Laureate; NU Outstanding Research and Creativity, 2013 UNMC Innovator of the Year, the 2014 Outstanding Faculty Mentor of Graduate Students and the Joseph Wybran Distinguished Scientist Awards. Dr. Gendelman was named a J. William Fulbright Research Scholar at the Weizmann Institute of Science in Israel. In 2001, he received the prestigious Jacob Javits Neuroscience Research Award from the National Institute of Neurological Disorders and Stroke and the Career Research Award in Medicine from the Department of Internal Medicine, UNMC.
He is included amongst a selective scientific group listed on highly cited.com as one of the top cited scientists in his field. Dr. Gendelman has trained more than forty scientists (students and postdoctoral fellows) who have themselves developed independent successful careers. Under his leadership, the department now holds scores of independent R01s or equivalent grants, four program project grants, and shares two program developmental awards. His leadership is credited with the growth of the Department of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center to be amongst the top-like ranked and federally funded departments (top ten) nationwide; a particularly noted feat as its position was 89 when he assumed its leadership.
The neuroregeneration laboratory provides the student or postdoctoral fellow with broad research experiences in diagnostics, pathogenic mechanisms and therapies for neurodegenerative disorders.
The major focus for our research is on the role played by glial inflammatory activities in brain disease. The work bridges immunology, neuroscience and pharmacology and crosses disease barriers for studies of HIV-1-associated neurocognitive disorders, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). The major goal is to use immune-based approaches to reverse nerve cell damage.
The laboratory initiative is divided into specific programs with cross-disciplinary support provided through experienced senior scientists. Specific expertise is available in proteomics, immunology, molecular neuroscience, infectious disease, neurophysiology and neuropathogenesis.
Research priorities in nanomedicine focuses on drug delivery to the central nervous system using "smart" drugs that are packaged into immunocytes and use “Trojan horse” cell-based mechanisms to by-pass the blood-brain barrier and enter diseased brain areas. These are intertwined with studies of disease pathogenesis focused on studies of the biophysical and effector cell properties of blood-borne macrophages that modulate leukocyte entry and glial immunity.
Our nanomedicine program provides laboratory experiences in nanoformulations and physical chemistry linked to characterization of nanoparticles as well as animal studies of disease pathobiology using "state of the art" drug delivery systems. Coordinate drug testing (anti-inflammatory, neuroprotective and anti-retroviral) in HIV-1 encephalitis (HIVE) and PD are pursued with adjunctive drugs distinct or part of the nanomedicine efforts.
This program is part of multiple National Institutes of Health grant efforts that involve scientists at the University of Nebraska Medical Center (College of Medicine and College of Pharmacy), the University of Rochester, and Columbia University College of Physicians and Surgeons. The focus is to perform translational research that would move quickly from animals to humans and currently involves human phase I testings.
Our neuroimmunologic and vaccine approaches have shown tremendous success in recent years for their abilities to induce protective immunity and protect against ongoing neurodegeneration. These are being pursued in animal models of HIVE, PD and ALS.
Our proteomic and metabolomic studies involve basic cell biology and molecular studies of virus-cell interactions in the setting of abused drugs.
All together this is a rich offering in scientific disciplines and relevant human disease models that can readily translate from the laboratory bench to the clinic.
- Thomas MB, Gnanadhas DP, Dash PK, Machhi J, Lin Z, McMillan J, Edagwa B, Gelbard H, Gendelman HE, Gorantla S. Modulating cellular autophagy for controlled antiretroviral drug release. Nanomedicine (Lond). 2018 Aug 21. doi: 10.2217/nnm-2018-0224. PMID: 30129397
- Montenegro-Burke JR, Woldstad CJ, Fang M, Bade AN, McMillan J, Edagwa B, Boska MD, Gendelman HE, Siuzdak G. Nanoformulated Antiretroviral Therapy Attenuates Brain Metabolic Oxidative Stress. Mol Neurobiol. 2018 Aug 1. doi: 10.1007/s12035-018-1273-8. PMID: 30069830
- Kevadiya BD, Woldstad C, Ottemann BM, Dash P, Sajja BR, Lamberty B, Morsey B, Kocher T, Dutta R, Bade AN, Liu Y, Callen SE, Fox HS, Byrareddy SN, McMillan JM, Bronich TK, Edagwa BJ, Boska MD, Gendelman HE. Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution. Theranostics. 2018 Jan 1;8(1):256-276. doi: 10.7150/thno.22764. eCollection 2018. PMID: 29290806. PMCID: PMC5743473.
- Li W, Gorantla S, Gendelman HE, Poluektova LY. Systemic HIV-1 infection produces a unique glial footprint in humanized mouse brains. Dis Model Mech. 2017 Dec 19;10(12):1489-1502. doi: 10.1242/dmm.031773. PMID: 29084769.
- McMillan J, Szlachetka A, Slack L, Sillman B, Lamberty B, Morsey B, Callen S, Gautam N, Alnouti Y, Edagwa B, Gendelman HE, Fox HS. Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: e01316-17. doi: 10.1128/AAC.01316-17. Print 2018 Jan. PMID: 29061742. PMCID: PMC5740312.
- Zhou T, Su H, Dash P, Lin Z, Dyavar Shetty BL, Kocher T, Szlachetka A, Lamberty B, Fox HS, Poluektova L, Gorantla S, McMillan J, Gautam N, Mosley RL, Alnouti Y, Edagwa B, Gendelman HE. Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials. 2018 Jan;151:53-65. doi: 10.1016/j.biomaterials.2017.10.023. Epub 2017 Oct 15. PMID: 29059541.
- Mosley RL, Gendelman HE. T cells and Parkinson's disease. Lancet Neurol. 2017 Oct;16(10):769-771. doi: 10.1016/S1474-4422(17)30276-4. Epub 2017 Aug 11. PMID: 28807669.
- Gendelman HE, Zhang Y, Santamaria P, Olson KE, Schutt CR, Bhatti D, Shetty BLD, Lu Y, Estes KA, Standaert DG, Heinrichs-Graham E, Larson L, Meza JL, Follett M, Forsberg E, Siuzdak G, Wilson TW, Peterson C, Mosley RL. Evaluation of the Safety and immunomodulatory Effects of Sargramostim in a Randomized, Double Blind Phase 1 Clinical Parkinson’s Disease Trial. NPJ Parkinsons Dis. 2017 Mar 23;3:10. PMID: 28649610. PMCID: PMC5445595.
- Gnanadhas DP, Dash PK, Sillman B, Bade AN, Lin Z, Palandri DL, Gautam N, Alnouti Y, Gelbard HA, McMillan J, Mosley RL, Edagwa B, Gendelman HE, Gorantla S. Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs. J Clin Invest. 2017 Mar 1;127(3):857-873. PMID: 28134625. PMCID: PMC5330738.
- Guo D, Zhou T, Araínga M, Palandri D, Gautam N, Bronich T, Alnouti Y, McMillan J, Edagwa B, Gendelman HE. Creation of a Long-Acting Nanoformulated 2’,3’Dideoxy-3’-Thiacytidine. J Acquir Immune Defic Syndr. 2017 Mar 1;74(3):375-e83. PMID: 27559685. PMCID: PMC5305294
- Bade AN, Gendelman HE, Boska MD, Liu Y.. MEMRI is a biomarker defining nicotine-specific neuronal responses in subregions of the rodent brain. Am J Transl Res. 2017 Feb 15;9(2):601-610. eCollection 2017. PMID: 28337287. PMCID: PMC5340694.
- Araínga M, Edagwa B, Mosley RL, Poluektova LY, Gorantla S, Gendelman HE. A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy. Retrovirology. 2017 Mar 9;14(1):17. doi: 10.1186/s12977-017-0344-7. PMID: 28279181. PMCID: PMC5345240.
- Heinrichs-Graham E, Santamaria PM, Gendelman HE, Wilson TW. The cortical signature of symptom laterality in Parkinson's disease. Neuroimage Clin. 2017 Feb 12;14:433-440. doi: 10.1016/j.nicl.2017.02.010. eCollection 2017. PMID: 28271041. PMCID: PMC5322212 .
- Edagwa B, McMillan J, Sillman B, Gendelman HE. Long-acting slow effective release antiretroviral therapy. Expert Opin Drug Deliv. 2017 Feb 6:1-11. doi: 10.1080/17425247.2017.1288212. PMID: 28128004. PMCID: PMC5545165
- Shahnaz G, Edagwa BJ, McMillan J, Akhtar S, Raza A, Qureshi NA, Yasinzai M, Gendelman HE. Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis. Nanomedicine (Lond). 2017 Jan;12(2):99-115. PMID: 27879160. PMCID: PMC5144491.
- Kevadiya BD, Bade AN, Woldstad C, Edagwa BJ, McMillan JM, Sajja BR, Boska MD, Gendelman HE. Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging. Acta Biomater. 2017 Feb;49:507-520. doi: 10.1016/j.actbio.2016.11.071. Epub 2016 Dec 1. PMID: 27916740. PMCID: PMC5501313.
- Embury CM, Dyavarshetty B, Lu Y, Wiederin JL, Ciborowski P, Gendelman HE, Kiyota T. Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer's Disease. J Neuroimmune Pharmacol. 2016 Dec 13. PMID: 27966067. PMCID: PMC5405105.