Pharmacology and Toxicology Faculty
NAME: Stephanie W. Watts
Educational Background
1983-88 B.S., Advanced Chemistry, The University of Illinois
1988-92 Ph.D., Pharmacology & Toxicology, Indiana University
1992-95 Postdoctoral Fellow, Physiology, The University of Michigan
1995-00 Assistant Professor, Pharmacology & Toxicology, Michigan State
University
2000-05 Associate Professor, Pharmacology & Toxicology, Michigan State
University
2005-present Professor, Pharmacology & Toxicology, Michigan State University
2008-present Assistant Dean, The Graduate School, Michigan State University
CONTACT INFO Email: wattss@msu.edu Lab: B445 Life Sciences Ph: 517-353-3724 Fax: 517-353-8915
BIOGRAPHY AND CURRENT RESEARCH
Research Synopsis:
Click to enlarge lab
Welcome! Our laboratory focuses on vascular smooth muscle pharmacology, physiology and
function. Our reasons for focusing on the vasculature are many, but include the important fact that the
vasculature is involved in numerous cardiovascular diseases. For example, hypertension affects
approximately 20-30% of the world‟s population, and hypertension continues to be a killer because it
places individuals at a higher risk for heart disease, stroke and kidney failure. Our laboratory is dedicated towards
understanding the mechanisms by which the vasculature contributes to this and other diseases. We have a history of
investigating „non-classical‟ pathways or signal transduction mechanisms for smooth muscle contraction. For example, 5-
hydroxytryptamine or 5-HT has long been disputed as having the ability to alter blood vessel tone in vivo; we take the
stance that it can and does so in very different ways than classically envisioned. . At the present, our laboratory has two
on-going established scientific projects, and we have just initiated a third that spreads our wings as a group dedicated to
understanding smooth muscle function. A final fourth area investigates vascular mechanisms of the peptide hormone
endothelin (ET).
1) Role of 5-HT (serotonin, 5-hydroxytryptamine) and the 5-HT transporter in control of normal arterial tone and blood
pressure; upregulation and altered function of 5-HT receptors in hypertension; determination of whether a local 5-HT
generating system exists in peripheral smooth muscle.
2) Serotonylation/amidation of proteins to send a biological signal (e.g. internal functions of 5-HT and norepinephrine)
3) Pharmacology of uterine and cervical smooth muscle.
We use a multi-faceted technical and integrated approach towards studying these diseases so as to understand the
mechanism from a molecular to a whole animal level. My goal for a student is that they have, in their hands, a set of
integrative techniques when they leave the lab such that they can explore pharmacological studies in a thoughtful,
interrogative manner. Techniques in our lab include: isolated tissue bath system to measure smooth muscle contraction,
myograph to measure small artery contraction, Western analyses and protein work, real time RT-PCR, Super Arrays,
pathway mapping based on gene arrays, HPLC, immunohistochemistry, immunocytochemistry, cell culture, kinase
assays, animal surgery, blood pressure measurement and, of course, pharmacology!
We are fortunate that our laboratory works closely with a number of other laboratories in the department, and our students
benefit tremendously for the collegial and exciting exchanges and progress made by our laboratories, collectively.
Current Projects (and the questions we want to answer):
1. Function of intracellular 5-HT and primary amines (how does 5-HT modify proteins?)
2. Alteration of 5-HT receptor subtype(s) in high pressure (do different subtypes upregulate?)
3. Mechanism of blood pressure fall to 5-HT in chronic infusion (how does this occur?)
4. Endothelin (ET) signaling in arteries and veins: heterodimerization of ETA and ETB receptor (do these two
receptors „talk‟ to one another and how does this change their pharmacology?)
5. Role of calcium in ET-induced vasoconstriction (are different calcium sources used in an artery vs a vein?)
6. Pharmacology of isolated uterine and cervical smooth muscle (is the profile of relaxants/contractants similar?
Different? How do these tissues work together)
SELECTED AWARDS AND ACHIEVEMENTS
Selected Achievements:
Editorial Boards
American Journal of Physiology: Heart, Lung and Circulatory
American Journal of Physiology: Regulatory, Integrative and Comparative
Clinical and Experimental Pharmacology and Physiology
Clinical Science, Associate Editor
Current Reviews of Hypertension
Frontiers in Vascular Physiology, Associate Editor
Hypertension
Journal of Pharmacology and Experimental Therapeutics, Associate Editor (thru 2009)
Molecular and Cellular Pharmacology (charter member, 2008)
Honors/Awards
PhRMA Faculty Development Award, 1998-2000
PhRMA Research Starter Award, 1998-2000
Young Scholar Award, American Society of Hypertension, 2001
Established Investigator of the American Heart Association, 2002
Howard Hughes Medical Investigator Nominee, Michigan State University, 2004
Bowditch Awardee of American Physiological Society, 2008 (Outstanding Research under age of 42)
COMMITTEES AND ACTIVITIES:
Committees/Service:
Member, Pharmaceutical Research and Manufacturers Association Foundation (PhRMA) Basic Pharmacology
Research Advisory Board, 2001-present
Pharmacology Study Section, NIH 2002-2004
Charter Member of Hypertension and Microbiology Study Section, NIH, NHLBI October 2004, 2004-2008
American Physiological Society, CV Section Nominating Committee, 2004-2007
ASPET Centennial Celebration Planning Committee, 2004-2008
Chair, ASPET Graduate Recruitment and Education Committee, 2005-2007
Vice-Chair, Hypertension Summer School, Maritime Academy in Maine, 2005
Chair, Hypertension 2007 Summer School (Ft. Collins, CO)
Chair, Trainee Advocacy committee, CHBPR , 2005-2007
Leadership of Council for High Blood Pressure research, 2005-2007, 2009.
• Chair of Keystone Conference “Dissecting the Vasculature”, held Feb 2009, Vancouver.
• Chair, NIH ZRG CVS-F (90S), AED.
• NIH RIBT Study Section (00201468), AHA SURF Peer Review Chair, NIH ZRG1 VH-D (58)R
Scientific review groups (2009); NIH RFA and F fellowship review committees (2010).
• AHA National Research Committee (2009)
• ASPET Cardiovascular Division Chair Elect (2011)
PUBLICATIONS AND ABSTRACTS (last 5 years)
•Thakali, K., Davenport, L., Fink, G. D. and Watts, S. W.: Pleiotropic effects of hydrogen peroxide in arteries and veins
from normotensive and deoxycorticosterone acetate-salt hypertensive rats, Hypertension, 47:482-487, 2006.
•Ni, W. and Watts, S. W.: 5-HT in the cardiovascular system: focus on the serotonin transporter (SERT), Clin. Exp.
Pharmacol. Physiol, 33:575-583, 2006.
•Thakali K. M., Lau, Y., Fink, G. D., Galligan, J. J., Chen, A. F. and Watts, S. W.: Mechanisms of hypertension
induced by nitric oxide (NO) deficiency: focus on venous function, J. Cardiovasc Pharmacol., 47:742-740, 2006.
•Ni, W., Lookingland, K. and Watts, S. W.: Arterial 5-HT transporter function is impaired in DOCA-salt hypertensive
but not spontaneously hypertensive rats, Hypertension, 48:134-140, 2006.
•Ogden, K., Thompson, J. M., Hickner, Z., Huang, T., Tang D. D. and Watts, S. W.: A new signaling paradigm for
serotonin: Use of Crk-Associated substrate in arterial contraction, Am. J. Physiology Heart Circ Phys, 291:H2857-
H2863, 2006.
•Ni, W.,Lookingland, L. and Watts, S. W.: Response to “Blood pressure in mutant rats lacking the 5-
hydroxytryptamine (5-HT) transporter, Hypertension, ePrint, Oct 2006.
•Szasz, T., Thakali, K., Fink, G. D. and Watts, S. W.: A comparison of arteries and veins in oxidative stress:
producers, destroyers, function and disease, Soc. Exp. Biol. Med, 232:27-37, 2007.
•Thakali, K., Davenport, L., Fink, G. D. and Watts, S. W.: Cyclooxygenase, p38 MAPK, Erk MAPK, Rho Kinase and
Src mediate hydrogen peroxide induced contraction of rat thoracic aorta and vena cava, J. Pharmacol. Exp. Ther.,
320:236-243, 2007.
•Rondelli, C. , Kayal, A., Szasz, T., Thakali, K., Watson, R. E., Rovner, A. S., Eddinger, T. J., Fink G. D. and Watts, S.
W. Preferential myosin heavy chain isoform B expression may contribute to the faster velocity of contraction in veins
vs arteries. J Vasc Res, 44:264-272, 2007.
• Watts, S. W., Rondelli, C., Thakali, K., Pervaiz, M., Watson, R. and Fink, G. D.: Morphologic and Biochemical
characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats, Am. J. Physiology Heart Circ,
292:H2438-2448, 2007.
•Ni, W, Fink, G. D. and Watts, S. W.: The 5-HT2A receptor is involved in (+) norfenfluramine-induced arterial conraction
and blood pressure increase in DOCA-salt hypertension, J. Pharmacol. Exp. Ther. 321:485-491, 2007.
•Fink, G. D., Li, M., Lau, Y., Osborne, J. and Watts, S. W.: Chronic activation of endothelin ETB receptors: A new
model of experimental hypertension, Hypertension, 50:512-518, 2007.
•Linder, A. E., Ni, W., Diaz, J. L., Szasz, T., Burnett, R. and Watts, S. W.: 5-HT in veins: not all in vain, invited
Perspectives in Pharmacology J. Pharmacol. Exp. Ther., 323:415-421, 2007.
•Linder, A.E., Thakali, K., Thompson, J., Watts, S. W., Webb, R. C. and Leite, R.: Methyl-b-cyclodextrin prevents
angiotensin II-induced tachyphylactic contractile responses in rat aorta, J Pharmacol Exp Ther., 323:78-84, 2007.
•Ogden, K. K., Falck, J. R. and Watts, S. W.: The cytochrome P450 inhibitor ketoconazole potentiates 5-
hydroxytryptamine-induced contraction in rat aorta, J. Pharmacol. Exp. Ther., 323:606-613, 2007.
• Watts, S. W., Thakali, K., Rondelli, C and Fink, G. D.: Processing of big ET-1 into vasoactive peptides: comparison
of arteries and veins, Vascular Pharmacology, 47:302-312, 2007.
•Huang J, Lin SC, Nadershahi A, Watts SW, Sarkar R.Role of redox signaling and poly (adenosine
diphosphate-ribose) polymerase activation in vascular smooth muscle cell growth inhibition by nitric oxide and
peroxynitrite., J Vasc Surg. 47(3):599-607, 2008.
•Linder, A. E., Diaz, J., Ni, W., Szasz, T., Burnett, R. and Watts, S. W.: Vascular reactivity, 5-HT uptake and
blood pressure in the serotonin transporter knockout rat, Am J Physiol Heart Circ Physiol, 294:H1745-H1752,
2008.
•Thakali, K., Galligan, J. J., Fink, G. D., Gariepy, C. E. and Watts, S. W.: Pharmacological endothelin receptor
interaction occurs in veins but not arteries, Vascular Pharmacology, 49:6-13, 2008.
•Ni, W, Geddes, T. J., Priestly, J. R. C., Szasz, T., Kuhn, D. M. and Watts, S. W.: The existence of a local
serotonergic system in peripheral arteries, Br J Pharmacol, 154:663-674, 2008.
• Diaz, J., Ni, W., King, A., Fink, G. D. and Watts, S. W.: 5-hydroxytryptamine lowers blood pressure in
normotensive and hypertensive rats. J Pharmacol Exp Ther, 325:1031-1038, 2008.
•Linder, A. E., Ni, W., Szasz, T., Burnett, R., Diaz, J., Geddes, T. J., Kuhn, D. M. and Watts, S.W.: A
serotonergic system in veins: serotonin-transporter independent uptake, J. Pharmacol. Exp. Ther., 325:714-
722, 2008.
•Ni, W., Zhou, H., Diaz, J., Murphy, D. L., Haywood, J. R. and Watts, S. W.: Lack of the serotonin transporter does
not prevent mineralocorticoid hypertension in rat and mouse, Eur. J Pharmacol, 589:225-227, 2008.
•Szasz, T., Thompson, J. M. and Watts, S. W.: A comparison of reactive oxygen species metabolism in aorta
and vena cava of the normal rat: focus on xanthine oxidase, Am J Physiol Heart Circ Physiol 295:H1341-
H1350, 2008.
•Watts, S. W.: The beginning of a fantastic, unanswered question: is 5-HT involved in systemic hypertension,
Am J Physiol Heart Circ Physiology, 295:H915-H916, 2008.
•Li, M., Dai, X., Watts, S.W., Kreulen, D. and Fink, G. D.: Increased superoxide levels in ganglia and
sympathoexcitation are involved in S6c-induced hypertension. Am J Physiol Reg Integr Comp Physiol, 295:R1546-
R1554, 2008.
•Watts, S. W.: The love of a lifetime: 5-HT in the cardiovascular system, Am J Physiol Reg Integr Comp
Physiol, 296:R252-R256, 2009. PMID 18753260
•Szasz, T., Eddy, S., Paulauskis, J., Burnett, R., Ellekilde, M., Iovanna, J. L. and Watts, S. W.: Arterial vs venous
expression of genes: differences in inflammatory genes, J Vasc Res, 46:551-560, 2009.
•Linder, A. E., Beggs, K., Burnett, R. and Watts, S. W.: Body distribution of infused serotonin in rats, Clin.
Exp Pharmacol. Physiol, 36:599-601, 2009.
•Tykocki, N.R., Gariepy. C.E. and Watts, S. W.: ETB receptors in arteries and veins: multiple actions in veins, J.
Pharmacol. Exp. Ther., 329:875-881, 2009.
•Watts, S. W., Priestley J.R. C. and Thompson, J. M.: Serotonylation of vascular protein important to contraction,
PLoS One, May 25, e5682, 2009.
•Watts SW: Endothelin receptors: what do we know and what do we need to know? Am J Physiol Regul Integr Comp
Physiol, 298:R254-R260, 2010.
•Seymour E. M., Watts, S. W.: Whole grape intake impacts cardiac PPAR and NFkB activity, fibrosis and
cytokine expression in rats with diastolic heart failure, Hypertension, 55:1179-1185, 2010.
•Szasz, T. and Watts, S. W.: Uric acid does not impact endothelial function of aorta from normotensive and DOCA-sal
hypertensive rats, J. Pharmacol. Exp. Ther., 333: 758-763, 2010.
•Linder, A. E., Gaskell, G. L., Szasz, T., Thompson, J. M. and Watts, S. W.: Serotonin receptors in the rat jugular vein:
presence and involvement in contraction, J. Pharmacol. Exp. Ther., 334:116-123, 2010.
•Tykocki, N. and Watts, S. W.: Calcium and ET, Clin Sci, 119:361-372, 2010.
•Szasz, T, Linder AE, Davis RP, Burnett, R., Fink, G. D. and Watts, S. W.: Allopurinol does not decrease blood
pressure or prevent the development of hypertension in the DOCA-salt model, submitted, J Cardiovasc Pharmacol,
56:627-634, 2010.
•Johnson, K. B., Thompson, J. M., and Watts, S. W.: Modification of proteins by norepinephrine is important for
vascular contraction, Frontiers in Vascular Physiology, Front. Physio. 1:131. doi: 10.3389/fphys.2010.00131
•Northcott, C., Watts, S. W., Chen, Y., Morris, M., Chen, A. F., and Haywood, J. R.: Small hairpin RNA adenoviral
inhibition of AT1A receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in
the rat. Am J Physiol Regul Integr Comp Physiol. Nov;299(5):R1202-1211, 2010.
•Invited Review: Watts SW and Davis P: 5-Hydroxtryptamine Receptors in Systemic Hypertension: an arterial focus,
Cardiovascular Therapeutics, 29:54-67, 2011.
•Ren W, Watts, S. W., Fanburg, B. L.: The serotonin transporter interacts with the PDGF (beta) receptor in PDGF-BB
induced signaling and mitogenesis in pulmonary artery smooth muscle cells. Am J Physiol. Lung Cell Mol Physiol,
300:L486-497, 2011.
•Davis, R., Linder A. E. and Watts, S W: Lack of the serotonin transporter (SERT) reduces the ability of 5-
hydroxytryptamine to lower blood pressure, Naunyn Schmied. Arch. Pharmacol, 383:543-546, 2011.
•Linder, A, Davis, R., Burnett, R. and Watts, S. W.: The serotonin transporter mediates vascular uptake of and
reactivity to serotonin in vessels from female rats, Clin. Exper. Pharmacol. Physiol., 38:314-322, 2011.
•Harrison, B., Watts, S.W. , Barrett, J. E., Coupet, J., Mazandarani, H., Nawoschik, S., Pangalos, M. N.,
Ramamoorthy, S., Schechter, L., Smith, D. L., Stack, G., Zhang, J., Zhange, G., Rosenzweig-Lipson, S. and Dunlop,
J.: Characterization of Vabicaserin (SCA-136), a functionally selective 5-HT2C receptor agonist, J. Pharmacol. Exp.
Ther., 337:673-680, 2011.
•Bush, C. J., Szasz, T., Johnson, K. B., Tykocki, N. R., Surewicz, W. K., Watson, R. E. and Watts, S. W.: Prior protein
is expressed in the vascular system, but recombinant human PrP does not protect vascular smooth muscle cells from
oxidative stress, accepted, Reinvention (Undergraduate Journal), 2011.
•Watts, S. W., Shaw, S., Burnett, R. and Dorrance, A. M.: Indoleamine 2,3-diooxygenase in perioaortic at:
mechanisms of inhibition of contraction, in press, Am. J. Physiol. Heart Circ. Physiol, 2011.
•Tan T, Watts, SW and Davis RP: Drug delivery: enabling technology for drug discovery and development.
IPRECIO micro infusion pump: programmable, refillable, and implantable. Front Pharmacol 2:44, Jul 29 2011.
•Davis RP, Pattison J, Thompson JM, Tiniakov R, Scrogin K
Updated 12/3/2011