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Jeffrey D. Hasday, MD

Dr. Herbert Berger Professor in Medicine

Academic Title:

Professor

Primary Appointment:

Medicine

Secondary Appointment(s):

BioChemistry&Molecular Biology, Pathology

Administrative Title:

Division Head, Pulmonary & Critical Care Medicine

Location:

110 S. Paca St., 2nd Floor

Phone (Primary):

(410) 328-8141

Fax:

(410) 328-0177

Education and Training

MD   University of Rochester, NY   1979

Internship   University of Rochester, NY   Medical    1980-1981

Residency  University of Rochester, NY – Medical    1981-1983

Fellow & Instructor    University of Rochester, Rochester, NY;  Department of Pharmacology and Toxicology   1979-1980

Clinical Fellow  University of Michigan Medical Center, Ann Arbor,  MI, Pulmonary & Critical Care; 1983-1984

Research Fellow    University of Michigan Medical Center, Ann Arbor, MI, Pulmonary & Critical Care; 1983-1984

Biosketch

Dr. Hasday is Board-certified in Internal Medicine, Pulmonary Medicine and Critical Care Medicine and is Head of the Pulmonary and Critical Care Medicine Division. He over 30 years experience as a pulmonary and critical care physician with clinical expertise in with acute lung injury/ARDS, sepsis/septic shock, interstitial lung disease, and asthma. His basic and translational research focuses on thermobiology, the effects of clinically relevant hypothermia and hyperthermia (including fever) on biological processes that contribute to homeostasis and disease pathogenesis. Specific research interests include p38 MAP kinase signaling and development of substrate-selective p38 inhibitors, TRPV4, endothelial barrier function, regulation of cytokine expression, acute lung injury, regulation of heat shock protein gene expression, therapeutic hypothermia in ARDS, and thermoregulation. Dr. Hasday also directs the University of Maryland Cytokine Core Laboratory

Research/Clinical Keywords

ARDS, ILD, IPF, interstitial lung disease, asthma, heat shock protein, p38 MAP kinase, endothelial, epithelial, cytokine, thermoregulation

Highlighted Publications

Singh IS, Viscardi RM, Kalvakolanu I, Calderwood S, Hasday JD. Inhibition of tumor necrosis factor-alpha transcription in macrophages exposed to febrile range temperature. A possible role for heat shock factor-1 as a negative transcriptional regulator. J Biol Chem. 2000 Mar 31;275(13):9841-8. PubMed PMID: 10734139.

Singh IS, He JR, Calderwood S, Hasday JD. A high affinity HSF-1 binding site in the 5'-untranslated region of the murine tumor necrosis factor-alpha gene is a transcriptional repressor. J Biol Chem. 2002 Feb 15;277(7):4981-8. PubMed PMID: 11734555.

Cooper ZA, Ghosh A, Gupta A, Maity T, Benjamin IJ, Vogel SN, Hasday JD, Singh IS. Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-{kappa}B recruitment to cytokine gene promoters. Am J Physiol Cell Physiol. 2010 Jan;298(1):C171-81. PubMed PMID: 19846753; PubMed Central PMCID: PMC2806152.

Cooper ZA, Singh IS, Hasday JD. Febrile range temperature represses TNF-alpha gene expression in LPS-stimulated macrophages by selectively blocking recruitment of Sp1 to the TNF-alpha promoter. Cell Stress Chaperones. 2010 Sep;15(5):665-73. PubMed PMID: 20221720; PubMed Central PMCID: PMC3006616.

Rice P, Martin E, He JR, Frank M, DeTolla L, Hester L, O'Neill T, Manka C, Benjamin I, Nagarsekar A, Singh I, Hasday JD. Febrile-range hyperthermia augments neutrophil accumulation and enhances lung injury in experimental gram-negative bacterial pneumonia. J Immunol. 2005 Mar 15;174(6):3676-85. PubMed PMID: 15749906.

Nagarsekar A, Greenberg RS, Shah NG, Singh IS, Hasday JD. Febrile-range hyperthermia accelerates caspase-dependent apoptosis in human neutrophils. J Immunol. 2008 Aug 15;181(4):2636-43. PubMed PMID: 18684954; PubMed Central PMCID: PMC2829976 

Shah NG, Tulapurkar ME, Damarla M, Singh IS, Goldblum SE, Shapiro P, Hasday JD. Febrile-range hyperthermia augments reversible TNF-α-induced hyperpermeability in human microvascular lung endothelial cells. Int J Hyperthermia. 2012;28(7):627-35. PubMed PMID: 22834633 

Tulapurkar ME, Almutairy EA, Shah NG, He JR, Puche AC, Shapiro P, Singh IS, Hasday JD. Febrile-range hyperthermia modifies endothelial and neutrophilic functions to promote extravasation. Am J Respir Cell Mol Biol. 2012 Jun;46(6):807-14. PubMed PMID: 22281986; PubMed Central PMCID: PMC3380289 

Gupta A, Cooper ZA, Tulapurkar ME, Potla R, Maity T, Hasday JD, Singh IS. Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release. J Biol Chem. 2013 Jan 25;288(4):2756-66. PubMed PMID: 23212905; PubMed Central PMCID: PMC3554941 

Tulapurkar ME, Ramarathnam A, Hasday JD, Singh IS. Bacterial lipopolysaccharide augments febrile-range hyperthermia-induced heat shock protein 70 expression and extracellular release in human THP1 cells. PLoS One. 2015;10(2):e0118010. PubMed PMID: 25659128; PubMed Central PMCID: PMC4320107 

Shah NG, Cowan MJ, Pickering E, Sareh H, Afshar M, Fox D, Marron J, Davis J, Herold K, Shanholtz CB, Hasday JD. Nonpharmacologic approach to minimizing shivering during surface cooling: a proof of principle study. J Crit Care. 2012 Dec;27(6):746.e1-8. PubMed PMID: 22762936; PubMed Central PMCID: PMC3494806 

Greenberg RS, Chen H, Hasday JD. Acetaminophen has limited antipyretic activity in critically ill patients. J Crit Care. 2010 Jun;25(2):363.e1-7. PubMed PMID: 19781895; PubMed Central PMCID: PMC2883688 

Potla R, Singh IS, Atamas SP, Hasday JD. Shifts in temperature within the physiologic range modify strand-specific expression of select human microRNAs. RNA. 2015 Jul;21(7):1261-73. PubMed PMID: 26018549; PubMed Central PMCID: PMC4478345 

Sonna LA, Kuhlmeier MM, Carter HC, Hasday JD, Lilly CM, Fairchild KD. Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study. Physiol Genomics. 2006 Jun 16;26(1):91-8. PubMed PMID: 16595739 

Fairchild KD, Singh IS, Carter HC, Hester L, Hasday JD. Hypothermia enhances phosphorylation of I{kappa}B kinase and prolongs nuclear localization of NF-{kappa}B in lipopolysaccharide-activated macrophages. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1114-21. PubMed PMID: 15972840 

Fairchild KD, Singh IS, Patel S, Drysdale BE, Viscardi RM, Hester L, Lazusky HM, Hasday JD. Hypothermia prolongs activation of NF-kappaB and augments generation of inflammatory cytokines. Am J Physiol Cell Physiol. 2004 Aug;287(2):C422-31. PubMed PMID: 15070815 

Afshar M, Richards S, Mann D, Cross A, Smith GB, Netzer G, Kovacs E, Hasday J. Acute immunomodulatory effects of binge alcohol ingestion. Alcohol. 2015 49(1):57-64(PMID: 25572859 

Hasday JD, Thompson C, Singh IS. Fever, immunity, and molecular adaptations. Compr Physiol. 2014 4:109-48 (PMID: 24692136).

 

Research Interests

Dr. Hasday’s laboratory made the following important contributions to biomedical science:

Described the effect of febrile-range hyperthermia (FRH) to reduce expression of tumor necrosis factor-alpha in macrophages and Kupffer cells. Specifically that TNF transcription was inhibited by FRH through three mechanisms: (1) repressor effect of HSF1 binding to TNF promoter; (2) TNF-specific reduction of NFkappaB recruitment to promoter chromatin; and (3) selective inhibition of Sp1 recruitment to TNF promoter. 

Showed that exposure to hyperthermia worsened lung injury and described the mechanisms, which include altered p38-dependent endothelial barrier function, increased epithelial apoptosis, and augmented neutrophil recruitment.

Showed that TLR signaling through p38 and heat shock signaling through HSF1 interact at the level of HSP72 chromatin to increase HSP72 expression and increasing HSP72 secretion and exosome release.

Dr. Hasday has published two recent clinical studies of temperature management in the ICU showing that acetaminophen is an ineffective antipyretic in critically ill patients, that cooling febrile ICU patients induces shivering and increases oxygen utilization by 60% and that shivering can be reduced by changing the temperature and body location of cooling pads.

Development of a new class of non-catalytic, substrate-selective p38 MAP kinase inhibitors using computer-aided drug design.

Dr. Hasday’s laboratory has described the cell biologic effects of clinically relevant hypothermia on NFkappaB activation, gene expression, and most recently, microRNA expression. In the most recent paper, he made the interesting finding that exposure activates a very small subset of genes (five) that converge on PKCalpha. By blocking PKCalpha, these hypothermia-activated genes relieve a cell cycle block and allow proliferation in lung epithelium, which may result in improved epithelial healing in vivo.

Dr. Hasday has completed a feasibility pilot study and has a planned multi-site randomized clinical trial of therapeutic hypothermia in patients with ARDS.

 

Grants and Contracts

 

4/13 – 6/17           National Institutes of Health R01HL69057: “p38 MAP kinase-dependent mechanisms of fever-enhanced acute lung injury” $250,000                           (annual direct costs) JD Hasday, co-PI (15%) (contact PI).

 

 

03/13 – 02/17        VA Merit Review IBX002143A “Hyperthermia-augmented epithelial apoptosis and acute lung injury.” $150,000 (annual direct costs)  

JD Hasday, PI (37.5% of VA effort).