Brian Giunta , MD, PhD
Assistant Professor, Center of Excellence for Aging & Brain Repair
Assistant Professor, Morsani College of Medicine Molecular Pharmacology & Physiology
Assistant Professor, Morsani College of Medicine Psychiatry and Behavioral Neurosciences
- PhD, Medical Science, University of South Florida College of Medicine ,USA - 2010.
- MS, Medical Science, University of South Florida College of Medicine ,USA - 2008.
- MD, Medicine, University Of South Florida , Tampa, United States - 2004.
- BS, Microbiology, University of South Florida ,USA - 1998.
Interdisciplinary & Emerging Signature Programs
- Allergy, Immunology & Infectious Disease, Neuroscience.
For the past 8 years my research has been focused on neuroinflammatory mechanisms underlying HIV associated cognitive disorders (HAND). and Alzheimer’s disease (AD). Both are fueled by a chronic neurodegenerative innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia with aging (please see our reviews: Mol Neurodegener.. 2011; CNS Neurol Disord Drug Targets. 2010; Drugs Future. 2009; and J Neuroinflammation. 2008. Our group was the first to discover HAART medications can both increase neuronal amyloidogenic APP processing, and reduce microglial clearance of the peptide (Mol Brain 2011). Currently we are focused on the role of chronic efavirenz containing regimens in advanced brain ageing as exemplified by accelerated cognitive deficits and AD like pathology in transgenic mice. This should provide pathophysiological insight in the deleterious, aging-like brain pathology, that may conferred by these medications and lay the basis to phase in less toxic HAART regimens in the future. Our early works involved creation of an in vitro model of HAND composed of cultured microglial cells synergistically activated by the addition of IFN-γ and the HIV-1 coat glycoprotein, gp120 (Brain Res Bull. 2004). We found this could be attenuated via the α7nAChR and p44/42 MAPK system with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA approved, and over time, have shown only minor improvement in neurodegenerative disease for a limited period, we next explored naturalcompounds that may attenuate HIV protein mediated inflammation and related pathology. This inflammation is a key moderator of Aβ plaque deposition in the brain. Indeed HIV-1 Tat-induced Aβ deposition, tau phosphorylation, and subsequent neuronal death could be risk factors for subsequent AD and/or HAND. As green tea-derived (-)-epigallocatechin-3-gallate (EGCG) can attenuate neuronal damage mediated by conditions such as brain ischemia, I investigated it’s therapeutic potential to mitigate neuronal damage characteristic of HAND (Brain Res. 2006; Am J Transl Res. 2009). EGCG treatment of primary neurons from normal mice reduced IFN-γ-enhanced neurotoxicity of gp120 and Tat by inhibiting JAK/STAT1 pathway activation. EGCG was also found to mitigate the neurotoxic properties of HIV-1 proteins in the presence of IFN- γ in vivo. Moreover we found fish oil can enhance the anti-amyloidogenic properties of EGCG in the Tg2567 mouse model of AD (Neurosci Lett. 2010). To explore the mechanism by which HIV may augment AD-like pathology, we found HIV-1 Tat protein inhibits microglial uptake of Aβ1-42 peptide, a process enhanced by IFN- γ and rescued by EGCG Int J. Clin. Exp. Pathol. 2008. To mimic the HAND clinical condition, we generated mice with HIV-1 Tat-induced AD-like pathology by cross-breeding HIV-1 Tat expressing mice with the PSAPP mouse model of AD. These mice showed significantly more Aβ deposition (neurodegeneration, neuronal apoptotic signaling, and phospho-tau than PSAPP mice (Int J Clin Exp Pathol. 2009). Additonally we haveexplored the role of CD45 in mouse models of AD (J Neurosci. 2011) and reviewed this immunomodulatorysystem (Mol Neurodegener. 2011) in terms of HIV cognitive disorders.
- Gold Humanism in Medicine Honor Society- Bahrnes/Benhke Chapter ( Member, 2011 - Present)
- American Society for Pharmacology and Experimental Therapeutics (ASPET) (Member, 2011 - Present)
- Society for Neuroimmune Pharmacology (Regular Member, 2010 - Present)
- Society for Neuroscience (Regular Member, 2008 - Present
Awards and Honors
- Dean’s Academic Performance Award (University of South Florida College of Medicine - 2009)
- Young Investigator Award in Drug Discovery, Development, and Regulatory Affairs (American Society for Pharmacology and Experimental Therapeutics (ASPET) - 2007)
- Emory University Future Leader in Psychiatry (Emory University - 2007)
- Anthony J. Reading M.D. Award for Outstanding Fourth Year Student in Psychiatry (University of South Florida College of Medicine - 2004)
- University of South Florida College of Arts and Sciences Honor Society (University of South Florida - 1996)
- Florida Academic Scholarship (State of Florida - 1994)
- THE ROLE OF HIV-1 TAT IN ALZHEIMER'S DISEASE ($148,043.00, 03/07/2008-02/28/2012)
- THE ROLE OF HIV-1 TAT IN ALZHEIMER'S DISEASE ($142,645.00, 03/07/2008-02/28/2012)
- THE ROLE OF HIV-1 TAT IN ALZHEIMER'S DISEASE ($145,303.00, 03/07/2008-02/28/2011)
- THE ROLE OF HIV-1 TAT IN ALZHEIMER'S DISEASE ($140,063.00, 03/07/2008-02/28/2009)
- Obregon, D.Hou, H.Deng, J.Giunta, B.Tian, J.Darlington, D.Shahaduzzaman, M.Zhu, Y.Mori, T.Mattson, MP.Tan, J. Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation.Nature communications. 3(): 777, 2012.
- Deng J, Hou H, Giunta B, Mori T, Wang YJ, Fernandez F, Weggen S, Araki W, Obregon D, Tan J. Autoreactive-Aβ antibodies promote APP β-secretase processing. J Neurochem.. 5(120): 732-740, 2012.
- Smith AJ, Giunta B, Shytle RD, Blum JM. Evaluation of a novel supplement to reduce blood glucose through the use of a modified oral glucose tolerance test. Am J Transl Res.. 2(3): 219-25, 2011.
- Giunta B, Ehrhart J, Obregon DF, Lam L, Le L, Jin J, Fernandez F, Tan J, Shytle RD. Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders. Mol Brain.. 1(4): , 2011.
- Salemi, J.Obregon, DF.Cobb, A.Reed, S.Sadic, E.Jin, J.Fernandez, F.Tan, J.Giunta, B. Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD).Molecular neurodegeneration. 6(1): 3, 2011.