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Jeffrey  D Hasday
 

Jeffrey D Hasday M.D.

Academic Title: Professor
Primary Appointment: Medicine
Secondary Appointments: Biochemistry and Molecular Biology, Pathology
Administrative Title: Division Head
JHASDAY@umaryland.edu
Location: Paca-Pratt Building 2N149
Phone: (410) 328-8141
Fax: (410) 328-0177

Research Interests:

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. His areas of clinical expertise are acute lung injury, sepsis, and interstitial lung diseases.

Dr. Hasday is internationally recognized for work on the immunomodulatory effects of physiologically relevant changes in temperature. His bedside-to-bench-to-bedside research on the basic mechanisms through which febrile-range hyperthermia (FRH) modulates host defenses has produced a substantial body of work in this area in the last decade.He recently reported that FRH dramatically increases pulmonary oxygen therapy. This work spans the range from the basic molecular and cell biology to whole animal models and clinical trials. If confirmed in humans, this will lead to a practice-altering ARDS study to originate from the Division. Dr. Hasday and colleagues at the University of Maryland have advanced a concept that fever borrows some heat-shock mechanisms, including the central heat-shock-activated transcription factor, Heat Shock Factor-1 (HSF-1), which act in different ways at febrile and heat-shock temperatures. His studies in HSF-1 knockout mice showing that heat shock increases lung inflammation and injury may lead to new therapeutic modalities.

Dr. Hasday has also showed that clinically-relevant hypothermia prolongs expression of the proinflammatory cytokines TNF and IL-1ß in monocyte cultures and blocks apoptosis in epithelial cells. He has recently shown that this effect is even more global in that activation of the pivotal transcription factor, NFkappaB, is prolonged in hypothermic cell. Since NFkappaB activates both proinflammatory cytokine genes and anti-apoptosis genes, this exciting finding may explain both the cytoprotective effects of hypothermia as well as its association with higher circulating cytokine levels and inreased mortality in patients with sepsis.


Publications:

Ensor JE, Wiener SM, McCrea KA, Viscardi RM, Hasday JD.  Differential effects of hyperthermia on macrophage interleukin-6 and tumor necrosis factor-alpha expression. Am J Physiol Cell Physiol 1994; 266:C967-C974.

Ensor JE, Crawford EK, Hasday JD.  Warming macrophages to the febrile range destabilizes tumor necrosis factor-alpha mRNA without inducing heat-shock.  Am J Physiol 1995; 269:C1140-C1146.

Hasday JD, Bascom R, Fitzgerald T, Dubin W.  Bacterial endotoxin is an active component of mainstream and sidestream cigarette smoke.  Chest 1999; 115:829-35.

Jiang Q, Detolla L, Kalvakolanu I, Fitzgerald B, Van Roojien N, Singh IS Hasday JD.  Febrile-range temperature modifies early systemic TNFa expression in bacterial endotoxin-challenged Mice. Infect. Immun. 1999 67:1539-46.

Jiang Q, Detolla L, Singh IS, Gatdula L, Fitzgerald B, Van Rooijen N, Cross AS, Hasday JD.  Exposure to febrile temperature upregulates expression of pyrogenic cytokines in endotoxin-challenged mice.  Am. J. Physiol. 1999; 276:R1653-R1660.

Jiang Q, Cross AS, Singh IS, Chen TT, Viscardi RM, Hasday JD. Febrile Core Temperature is Essential for Optimal Host Defense in Bacterial Peritonitis. 2000; Infect. Immun., 68:1265-70.

Singh IS, Calderwood S, Kalvakolanu I, Viscardi RM, Hasday JD. Inhibition of  Tumor Necrosis Factor-a 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, 275:9841-48

Hasday JD, Fairchild K, Shanholtz C. The Influence of Fever on Survival in Sepsis. 2000; Microbes and Infection; 15:1891-1904.

Hasday JD, Bannerman D, Sakarya S, Singh IS, Howard D, Drysdale B-E, and Goldblum SE. Exposure to Febrile Temperature Modifies Endothelial Cell Response to Tumor Necrosis Factor-a. 2001; J. Appl. Physiol; 90:90-98.

Fairchild K, Viscardi RM, Hester L, Singh IS, and Hasday JD. Effects of Hypothermia and Hyperthermia on Cytokine Production by Cultured Human Mononuclear Phagocytes from Adults and Newborns. 2000; J. Interferon Cytokine Res.; 20:1049-55.

Hasday JD and Singh. Fever and the Heat Shock Response: Distinct Partially Overlapping Processes. 2000; Cell Stress & Chaperones; 5:471-80.

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-a gene is a transcriptional repressor. J Biol Chem. 2002; 277:4981-4988.

Hasday JD, Garrison A, Standiford T,  Rao S, He J-R, Rice P, Frank M,  Goldblum SE, and Viscardi RM. Febrile-Range Hyperthermia Enhances Neutrophil-Dependent Pulmonary Oxygen Toxicity. Am. J. Pathol. 2003; 162:2005-2017.

Singh IS, He J-R, Hester L, Fenton MJ, HasdayJD. Bacterial endotoxin modifies heat shock factor-1 activity in RAW 264.7 cells: implications for TNF-alpha regulation during exposure to febrile range temperatures. J Endotoxin Res. 2004;10(3):175-84.

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

Ellis GS, Carlson D, Hester L, Bagby G, He J-R, and Hasday JD. G-CSF, but Not Corticosterone Mediates Circulating Neutrophilia Induced by Febrile Range Hyperthermia. 2005; J. Appl Physiol. 98:1799-804.

Nagarsekar A, Hasday JD, and Singh IS. CXC chemokines: A new family of heat-shock proteins? Immunologic Investigations. 2005; 34:381-98.

Fairchild KD, Singh IS, Carter HC, Hester L, Hasday JD. Hypothermia enhances phosphorylation of I kappa B kinase andprolongs nuclear localization of NF-kappa B in LPS-activated macrophages. Am J Physiol Cell Physiol. 2005; 289: C1114-21.