Research Summary

Since the beginning of the AIDS epidemic, I have been involved in studying the role of macrophages in the pathogenesis of a wide variety of diseases, including neurodegenerative diseases and cancer. The primary model systems for these studies revolved around the study of HIV-infected macrophages and their influence on the brain, as well as in lymphoma. Through the study of HIV, I have gained important insight into the pathogenesis of other non-HIV diseases that seem to operate in the same manner as those associated with HIV infection. A critical component of the studies performed over the past 30 years was the creation of the ACSR, a central NCI-sponsored program of which I have been the PI since 1994. Access to well-preserved tissues from patients with a wide variety of AIDS-related conditions has allowed the discovery of fundamental mechanisms of disease that would never have been made otherwise. Through study of ACSR specimen sets, we have discovered that HIV-infected macrophages persist in tissues long after the blood has been cleared of infectious HIV. In fact, recent evidence suggests that infected macrophages play central roles in the pathogenesis of major post-cART diseases, such as cancer and heart disease. The current ACSR program will continue to expand investigator access to biospecimens for HIV-associated cancer research.

Research Funding

  • September 18, 2019 - August 31, 2024 - Pathogenesis of the cART unresponsive Kaposi?s sarcoma tumor niche , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA239263
  • September 23, 2013 - August 31, 2024 - AIDS and Cancer Specimen Resource (ACSR) , Principal Investigator . Sponsor: NIH, Sponsor Award ID: UM1CA181255
  • September 4, 2013 - July 31, 2019 - Molecular Features of and Approach to the HIV CNS Reservoir Post cART , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01MH100984
  • September 13, 2002 - August 31, 2016 - AIDS and Cancer Specimen Resource Central Office and Data Coordinating Center , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA096230
  • September 30, 1994 - August 31, 2014 - West Coast AIDS and Cancer Specimen Resource (ACSR) , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA066529
  • May 24, 2007 - October 31, 2013 - Macrophage Targeted Therapy for HAD and HIV Disease , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U19MH081835
  • February 14, 2005 - January 31, 2010 - HIV Sequence Evolution in AIDS Dementia Pathogenesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01MH073510
  • August 1, 2004 - December 31, 2005 - Endogenous Retrovirus Herv-K in Lymphoma and ALS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R41CA105744
  • April 1, 1995 - January 31, 2001 - PATHOGENESIS OF HIV INTEGRATED LYMPHOMA , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA067381
  • April 1, 1991 - March 31, 2000 - ANTIGENIC SPECIFICITY AND V REGION USE OF AIDS B NHLS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA054743

Education

University of Minnesota, B.S., 1974, Biology Medicine
Stanford University School of Medicine, M.D., 1980, Medicine
Stanford University School of Medicine, Ph.D., 1981, Cancer Biology

Honors & Awards

  • 1990
    Outstanding Speaker Award, American Association for Clinical Chemistry
  • 1999-2000
    Mercatur Scholar, University of Heidelberg, Germany

Selected Publications

  1. McGrath MS, Zhang R, Bracci PM, Azhir A, Forrest BD. Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression. Biomedicines. 2024 Oct 16; 12(10).  View on PubMed
  2. Forrest BD, Goyal NA, Fleming TR, Bracci PM, Brett NR, Khan Z, Robinson M, Azhir A, McGrath M. The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis. Biomedicines. 2024 Oct 16; 12(10).  View on PubMed
  3. Scholte LLS, Browne J, Nolan DJ, St John P, Tracy K, Thur RS, Li G, Lamers SL, Bracci P, McGrath MS, Bethony JM. Protocol for the simultaneous isolation of DNA, RNA, and miRNA from a single archived Kaposi sarcoma biopsy. STAR Protoc. 2024 Dec 20; 5(4):103365.  View on PubMed
  4. Zhang R, Bracci PM, Leong A, Rapp C, McGrath MS. Utility of an Archival Dried Blood Spot (DBS) Collection from HIV-Infected Individuals with and without Cancer in a Resource-Limited Setting. Int J Mol Sci. 2024 Sep 24; 25(19).  View on PubMed
  5. Lamers SL, Fogel GB, Liu ES, Nolan DJ, Rose R, McGrath MS. HIV-1 subtypes maintain distinctive physicochemical signatures in Nef domains associated with immunoregulation. Infect Genet Evol. 2023 11; 115:105514.  View on PubMed
  6. McGrath MS, Zhang R, Bracci PM, Azhir A, Forrest BD. Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS. Cells. 2023 03 28; 12(7).  View on PubMed
  7. Nolan DJ, Rose R, Zhang R, Leong A, Fogel GB, Scholte LLS, Bethony JM, Bracci P, Lamers SL, McGrath MS. The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi's Sarcoma Tumors during Antiretroviral Therapy. Viruses. 2022 12 13; 14(12).  View on PubMed
  8. Zhang R, Bracci PM, Azhir A, Forrest BD, McGrath MS. Macrophage-Targeted Sodium Chlorite (NP001) Slows Progression of Amyotrophic Lateral Sclerosis (ALS) through Regulation of Microbial Translocation. Biomedicines. 2022 Nov 12; 10(11).  View on PubMed
  9. Miller RG, Zhang R, Bracci PM, Azhir A, Barohn R, Bedlack R, Benatar M, Berry JD, Cudkowicz M, Kasarskis EJ, Mitsumoto H, Manousakis G, Walk D, Oskarsson B, Shefner J, McGrath MS. Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses. Muscle Nerve. 2022 07; 66(1):39-49.  View on PubMed
  10. Markazi A, Meng W, Bracci PM, McGrath MS, Gao SJ. The Role of Bacteria in KSHV Infection and KSHV-Induced Cancers. Cancers (Basel). 2021 Aug 25; 13(17).  View on PubMed
  11. Markazi A, Bracci PM, McGrath M, Gao SJ. Pseudomonas aeruginosa Stimulates Inflammation and Enhances Kaposi's Sarcoma Herpesvirus-Induced Cell Proliferation and Cellular Transformation through both Lipopolysaccharide and Flagellin. mBio. 2020 11 10; 11(6).  View on PubMed
  12. Ljubenkov PA, Miller Z, Mumford P, Zhang J, Allen IE, Mitic L, Staffaroni A, Heuer H, Rojas JC, Cobigo Y, Karydas A, Pearlman R, Miller B, Kramer JH, McGrath MS, Rosen HJ, Boxer AL. Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency. Front Neurol. 2019; 10:1004.  View on PubMed
  13. Maguire A, Chen X, Wisner L, Malasi S, Ramsower C, Kendrick S, Barrett MT, Glinsmann-Gibson B, McGrath M, Rimsza LM. Enhanced DNA repair and genomic stability identify a novel HIV-related diffuse large B-cell lymphoma signature. Int J Cancer. 2019 12 01; 145(11):3078-3088.  View on PubMed
  14. Lamers SL, Fogel GB, Nolan DJ, Barbier AE, Rose R, Singer EJ, Gonzalez-Perez MP, McGrath MS. Emerging Patterns in HIV-1 gp120 Variable Domains in Anatomical Tissues in the Absence of a Plasma Viral Load. AIDS Res Hum Retroviruses. 2019 06; 35(6):588-596.  View on PubMed
  15. Jin X, Xu H, McGrath MS. Methylglyoxal-bis-guanylhydrazone inhibits osteopontin expression and differentiation in cultured human monocytes. PLoS One. 2018; 13(3):e0192680.  View on PubMed
  16. Nolan DJ, Rose R, Rodriguez PH, Salemi M, Singer EJ, Lamers SL, McGrath MS. The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2018 01; 34(1):123-125.  View on PubMed
  17. Lamers SL, Fogel GB, Liu ES, Barbier AE, Rodriguez CW, Singer EJ, Nolan DJ, Rose R, McGrath MS. Brain-specific HIV Nef identified in multiple patients with neurological disease. J Neurovirol. 2018 02; 24(1):1-15.  View on PubMed
  18. Rose R, Nolan DJ, Maidji E, Stoddart CA, Singer EJ, Lamers SL, McGrath MS. Eradication of HIV from Tissue Reservoirs: Challenges for the Cure. AIDS Res Hum Retroviruses. 2018 01; 34(1):3-8.  View on PubMed
  19. Nolan DJ, Lamers SL, Rose R, Dollar JJ, Salemi M, McGrath MS. Single Genome Sequencing of Expressed and Proviral HIV-1 Envelope Glycoprotein 120 (gp120) and nef Genes. Bio Protoc. 2017 Jun 20; 7(12):e2334.  View on PubMed
  20. Lakritz JR, Yalamanchili S, Polydefkis MJ, Miller AD, McGrath MS, Williams KC, Burdo TH. An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy. J Neurovirol. 2017 08; 23(4):568-576.  View on PubMed

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