Ph.D., Johns Hopkins University, 1984

The following research projects on airway and vascular smooth muscle cells are potentially significant for understanding the basic mechanisms of inflammatory airway diseases such as asthma, and prolifierative vascular diseases such as atherosclerosis.

Systems Biology of Inflammatory Gene Expression in Airway Smooth Muscle:
Airway smooth muscle cells produce multiple inflammatory products in response to multiple inflammatory stimuli. This project tests the hypothesis that Erk1/2, p38, and JNK MAPK kinases, MAPK phosphatase, and COX enzymes are the core processes that regulate redundancy, robustness, and temporal dynamics in the system of inflammatory gene expression. Experimental approaches include the measurement of inflammatory gene expression by real-time RT-PCR, Western blotting, and immuno-histochemistry. Mathematical approach includes kinetic modeling using WinSAAM (Windows version of Simulation, Analysis, and Modeling).

Regulation of Podosome Dynamics in Vascular Smooth Muscle Cells:
Podosomes are cytoskeletal structures that regulate the release of metalloproteinase and degradation of the extracellular matrix. Therefore, podosomes are potentially important for proliferative vascular diseases such as atherosclerosis. This project tests the hypothesis that PKC, Erk1/2 MAPK, and caldesmon regulate podosome dynamics in vascular smooth muscle cells. PKC and Erk1/2 MAPK are signaling molecules involved in the regulation of podosome dynamics. Caldesmon is an actin-binding protein involved in the regulation of actin cytoskeletal remodeling and contractility. Erk1/2 MAPK and caldesmon are both regulated by phosphorylation. Experimental approaches include cell culture, overexpression of mutant proteins by transfection confocal immuno-fluorescence microscopy, live-cell imaging, scanning electron microscopy, and Western blotting.

2008-Present Course Leader Biomed 116 Exercise Physiology
2007-Present Course Leader Biomed 80 Principles of Physiology
1991-2007 Lecturer Biomed 80 Principles of Physiology
1991-92 Course Leader Biomed 80 Principles of Physiology
1994-95 Course Leader Biomed 110 Cell Physiology and Biophysics
2003-04 Lecturer Biomed 113 Cell Structure and Movement
1989-06 Course Leader Biomed 117 Mammalian Physiology
1989-90 Lecturer Biomed 118 Comparative Physiology
1992-93 Seminar Speaker Biomed 209 Special Topics in Respiratory Physiology
2006 Lecturer Biomed 217 Molecular Pharmacology & Physiology

Independent Studies (Since Tenure in 1994)
1994-2008 ~41 Students (28 received honors, and 3 received prizes)
2005 David Beck, Recipient of Morris L. Povar Prize in Physiology or
Zoology
1999 Jennifer Zander, Recipient of Morris L. Povar Prize in Physiology or Zoology
1995 Edwin Cadet, Recipient of Morris L. Povar Prize in Physiology or Zoology

Ph.D. Graduates Directed
2007 Zhizhan Gu, Post-doctoral Fellow, Harvard Medical School
2006 Hak Rim Kim, Post-doctoral Fellow, Boston University
2000 Steven An, Assistant Professor, Johns Hopkins School of Public Health

Cell Physiology and Biophysics (BIOL1100)
Cell Structure and Movement (BIOL1130)
Comparative Animal Physiology (BIOL1180)
Mammalian Physiology (BIOL1170)
Molecular Pharmacology and Physiology (BIOL2170)
Principles of Exercise Physiology (BIOL1160)
Principles of Physiology (BIOL0800)
Special Topics in Respiratory Physiology (BIOL2090)

• Hai, C.-M. Mechanistic systems biology of inflammatory expression in airway smooth muscle as tool for asthma drug development. Curr. Drug. Discovery Technol., 2008 (Accepted for Publication)
• Hai, C.-M. Caldesmon as a therapeutic target for proliferative vascular diseases. Mini-Reviews in Medicinal Chemistry 8: 1209-1213, 2008
• Hai, C.-M. Airway smooth muscle cell as therapeutic target of inflammation. Curr. Med. Chem. 14: 67-76, 2007
• Gu, Z., J. Kordowska, G.L. Williams, C.-L.A. Wang, and C.-M. Hai. Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. Exp. Cell Res. 313: 849-866, 2007
• Kanefsky, J., M. Lenburg, and C.-M. Hai. Cholinergic receptor and cyclic stretch-mediated inflammatory gene expression in intact ASM. Am. J. Respir. Cell Mol. Biol. 34: 417-425, 2006
• Hai, C.-M. and Z. Gu. Caldesmon phosphorylation in actin cytoskeletal remodeling. Eur. J. Cell Biol. 85: 305-309, 2006.
• Kim, H.R. and C.-M. Hai. Mechanisms of mechanical strain memory in airway smooth muscle. Can. J. Physiol. Pharmacol. 83: 811-815, 2005
• Hai, C.-M. and H.R. Kim. An expanded latch-bridge model of protein kinase C-mediated smooth muscle contraction. J. Appl. Physiol. 98:1356-1365, 2005
• Lu, Q., E.O. Harrington, C.-M. Hai, J. Newton, M. Garber, T. Hirase, and S. Rounds. Isoprenylcysteine carboxyl methyltransferase modulates endothelial monolayer permeability. Involvement of RhoA carboxyl methylation. Circ. Res., 94: 306-315, 2004.
• Kim, H.R., M. Hoque, and C.-M. Hai. Cholinergic receptor-mediated differential cytoskeletal recruitment of actin- and integrin-binding proteins in intact airway smooth muscle. Am. J. Physiol.: Cell Physiol. 287:.C1375-C1383, 2004
• Wahl, M. and C.-M. Hai. Sinusoidal length oscillation and receptor-mediated mRNA expression of myosin isoforms and alpha-SM actin in airway smooth muscle. Am. J. Physiol. Cell Physiol. 287: C1697-C1708, 2004
• Bai, T.R. et al. On the terminology for describing the length-force relationship and its changes in airway smooth muscle. J. Appl. Physiol. 97: 2029-2034, 2004.
• Hai, C.-M., G. Sadowska, L. Francois, and B.S. Stonestreet. Maternal Dexamethasone Treatment Modulates Myosin Isoform Expression and Contractile Dynamics in Fetal Carotid Arteries. Am. J. Physiol. Heart Circ. Physiol. 283: H1743-H1749, 2002.
• Hai, C.-M., P. Hahne, E.O Harrington, and M. Gimona. Conventional PKC mediates phorbol dibutyrate-induced cytoskeletal remodeling in A7r5 smooth muscle cells. Experimental Cell Research, 280:64-74, 2002.
• Silberstein, J. and C.-M. Hai. Dynamics of length-force relations in airway smooth muscle. Respiratory Physiology & Neurobiology 132: 205-221, 2002.
• Chan, W.L., J. Silberstein, and C.-M. Hai. Mechanical strain memory in airway smooth muscle. Am. J. Physiol. Cell Physiol. 278: C895-C904, 2000.
• An, S.S. and C.-M. Hai. Mechanical signals and mechanosensitive modulation of intracellular [Ca2+] in smooth muscle. Am. J. Physiol. Cell Physiol. 279: C1375-C1384, 2000.
• Hai, C.-M. Mechanosensitive modulation of receptor-mediated crossbridge activation and cytoskeletal organization in airway smooth muscle. Arch. Pharmacal Res. 23: 535-547, 2000.
• An, S.S. and C.-M. Hai. Mechanical Strain Modulates Maximal Phosphatidylinositol Turnover in Airway Smooth Muscle. Am. J. Physiol 277 (Lung Cell. Mol. Physiol. 21): L968-L974, 1999.
• Wong, C.T. and C.-M. Hai. Mucosal modulation of agonist-induced myosin phosphorylation and contraction in airway smooth muscle. Respiration Physiology 115: 103-111, 1999.
• Youn, T., S.A. Kim, and C.-M. Hai. Length-dependent modulation of smooth muscle activation: effects of agonist, cytochalasin, and temperature. Am. J. Physiol. 274 (Cell Physiol. 43): C1601-1607, 1998.
• Tseng, S., R. Kim, T. Kim, K.G. Morgan, and C.-M. Hai. F-actin disruption attenuates agonist-induced [Ca2+], myosin phosphorylation, and force in smooth muscle. Am. J. Physiol. 272 (Cell Physiol. 41): C1960-C1967, 1997.
• Szeto, B. and C.-M. Hai. Length-dependent modulation of myosin phosphorylation and contractile force in coronary arterial smooth muscle. Arch. Biochem. Biophys. 329: 241-248, 1996.
• Yoo, J., R. Ellis, K.G. Morgan, and C.-M. Hai. Mechanosensitive modulation of myosin phosphorylation and phosphatidylinositol turnover in smooth muscle. Am. J. Physiol. 267 (Cell Physiol. 36): C1657-C1665, 1994.