Quality Control Project

Beth Ann Murphy

**** ****** **** ****

Edison, New Jersey 08820

(H): 908-***-**** (W): 732-***-****

Email: ***********@*****.***

EDUCATION:

UMDNJ/ Rutgers University, Newark, New Jersey

PhD: Integrative Neuroscience Program, 2009.

Dissertation Title: Nutrient Regulation of Hypothalamic

Glucose Sensing Neurons

Advisor: Dr. Vanessa Routh

Seton Hall University, West Orange, New Jersey

M.S. Microbiology, 1993

Research and interest: the progression and treatment of

endotoxin induced septic shock.

Muhlenberg College Allentown, Pennsylvania

B.S. Biology, 1987

WORK EXPERIENCE:

Merck Research Laboratories, Rahway, New Jersey

Department of Pharmacology (1995-2008) In vivo Pharmacology (2008-Present)

. Research Associate (1995-2007); Senior Research Scientist (2007-2011);

Research Fellow (Present)

. Leads a group whose purpose is to establish, validate and implement

in vivo disease models to support a variety of investigational

therapeutic targets. Creates in vivo pharmacodynamic assays by

integrating knowledge of scientific literature and general

physiology with target-specific biological activities. Investigates

new technologies and methodology to improve the reliability, the

efficiency and relevance of in vivo assays currently utilized.

Responsible for coordinating and supervising activities of multiple

scientific and technical staff.

o Obesity (1995-2000;Present)

. Established appropriate in vivo models to support novel

Obesity-Directed Therapeutic Targets.

. Introduced rodent food intake, body weight and body

composition measurements to study anti-obesity agents.

. Pioneered the use of simultaneous and continuous

feeding, drinking, activity and temperature measurements

to understand the behavioral and physiological effects

of anti-obesity agents.

. Introduced the use intra-cerebroventricular injections

in rodents to the Merck research community.

. Spear headed efforts to establish a marmoset obesity

model.

. Studied the roles of melanocortins, serotonin, leptin

and NPY have in causing obesity.

. Coordinates all aspects of metabolic rate studies using

indirect calorimetry. Responsible for equipment

operation and maintenance, study design, data

collection, analysis and presentation.

o Atherosclerosis (Present)

. Established, optimized and standardized in vivo models

to support target identification/validation efforts

using multiple platforms (shRNA, siRNA, small molecule)

for the Atherosclerosis franchise.

. Manages a portfolio of assays used to guide Medicinal

Chemistry Programs in the Lead Optimization Space.

o Diabetes (Present)

. Uses the murine oral glucose tolerance test to evaluate

anti-diabetogenic agents.

. Uses understanding of glucose homeostasis and the

process of diabetes pathology to tailor the GTT paradigm

for each specific target (e.g. diet modification,

fasting time, etc.).

o Pain ( 2002-2005)

. Applied rodent models of neuropathic and inflammatory

pain to study potential therapeutic pain targets.

. Proficient in sciatic and spinal nerve ligation

surgeries and determining both mechanical and thermal

pain thresholds in mice and rats

. Established the pain phenotypes of genetically

engineered mice.

o Anxiety and Depression (2001-2002)

. Set up rodent models of anxiety and depression (i.e.

tail suspension test and light/dark test).

. Determined the relationship between estrus cycle and

anxiety and depression readouts.

. Studies the effect of estrogen replacement to

ovariectomized mice on anxiety and depression.

. Investigated the role of estrogen in modulating feeding,

body composition and temperature.

o Peri-menopausal Hot Flush (2000-2001)

. Established the morphine dependent ovariectomized rat

model for menopausal hot flush.

o Wound Healing and Angiogenesis (1993-1995)

. Developed and applied of animal models of

neoangiogenesis and tumor growth

. Evaluated the role of growth factors in dermal wound

healing and tumor growth.

. Demonstrated the angiogenic properties of several growth

factors in a rat model of corneal angiogenesis.

. Demonstrated that importance of VEGF activity in tumor

growth using an anti-VEGF antibody in a solid tumor

model in Nude mice.

o Infectious Diseases (1992-1993)

. Evaluated antibacterial efficacy using standard rodents

bacterial challenge assays.

. Leadership Roles

o Serves as the in vivo representative on project strategy

teams across the basic research space.

. Across multiple stages of the research process (Target

Identification to Lead Optimization)

. Across multiple Metabolic Syndrome related therapeutic

areas (Diabetes, Obesity, Atherosclerosis

. Advises, collaborates and coordinates in vivo biology

efforts for specific project teams.

. Manages and optimizes the use of multiple in vivo test

platforms.

o Manages the daily activities of multiple scientific staff.

. Other Areas of Expertise

o Developed and implemented an in vitro hypothalamic release

assay to investigate the effect of anti-obesity agents on

neuropeptide release.

o Established technique using membrane potential sensitive dye

to rapidly determine the activity of large neuronal

populations.

o Implemented use of the Biobook data analysis software package

to service several screening platforms.

. Other technical skills

o Performed routine pharmacokinetic studies in Chimpanzees,

Rhesus monkeys, and rodents.

o Performed routine toxicological screens in mice.

o Proficient in routine in vitro techniques (RIA, EIA).

o Proficient in dosing and handling of a wide range of species

(mouse, rat, ferret, monkey, rabbit).

o Adept at primary neuronal cell culture.

Prior Work Experience

Smith Kline Beecham Pharmaceuticals, Piscataway, New Jersey

1988- 1992

. Microbiologist

o Responsibilities included performing routine quality control

Microbiological testing of parenternal medications. Routinely

performed sterility testing, LAL pyrogen testing and microbial

limits testing. Other tasks include meticulous record keeping as

well as editing, updating and developing procedures

PROFESSIONAL SOCIETIES:

. American Society of Microbiology: 1988-1992

. American Association of Laboratory Animal Scientists: 1993-1995

o Certified AALAS Laboratory Animal Technician, 1993.

. Society for Neuroscience, 1999- Present.

. American Physiological Society (2004-Present)

COURSES AND TRAINING:

. Mouse Behavioral Analysis Course, Cold Spring Harbor, 2002.

AWARDS & HONORS:

. SmithKline Beecham Directors Impact Award (1990)

. Various awards recognizing research excellence in MRL (2004-present).

. Selected for the Merck Doctoral Study Program (2005-2007)

SERVICE:

. Ad hoc reviewer for American Journal of Physiology

. Lecturer for the Neurosurgery Resident Lecture Series, UMDNJ, Newark,

NJ

. Merck UNCF Summer Intern Mentor (1999-2000).

. Merck Summer Intern Mentor (2009)

References Furnished Upon Request

ABSTRACTS/ PRESENTATIONS:

J.J .Jackson, J.G. Sundelof, C.J. Gill, B. Stark Murphy, and H. Kropp. In

Vivo Activity of L-739,428 (BO-2727) in Murine Septicemia and Tissue

Infection Models. 32nd ICAAC, October, 1992.

J.G. Sundelof, C. Gill, B. Stark Murphy, R. Thompson, R. Hajdu and H.

Kropp and A. Hisaka, Y. Sawasaki, A. Fuse, M. Sanada, and S. Nakagawa.

Comparative Pharmacokinetics of Carbapenem, BO-2727 (L-739,428), in

Primates and Disposition in Rodents. 32nd ICAAC, October, 1992.

R. Hajdu, R. Thompson, K. White, BA Murphy, and H. Kropp. Comparative

Pharmacokinetics of Three Water-Soluble Analogues of the Lipopeptide

Antifungal Compounds L-688-786 in Mice and Rhesus Monkeys. 33rd ICAAC,

October, 1993.

JS Mudgett, EK Bayne, NA Chartrain, A. Christen, NI Hutchinson, DW Kawka, J

McDonnell, T Mellin, BA Murphy, C Orevillo, J.Ronan, J Sargeant, CF Shen, I

Singer, DM Visco. Characterization of the Stromelysin-1 (MMP3) Knockout

Mouse. Gordon Conference, 1995.

BA Murphy, TN Mellin, CN Nunes, JJ Ronan, CM Harper, MJ Beall, MJ Hanaway,

LHT Van der Ploeg and DE MacIntyre. Characterization of Melanocortins on

Feeding, Behavior in Rats. 8th International Congress on Obesity, Paris,

France (1998).

BA Murphy, CN Nunes, AM Fairhurst, MJ Hanaway, and TN Mellin. Effect of the

Melanocortin Receptor Agonist, MTII, on Rat Feeding Behavior and Other

Physiological Parameters Measured by Remote Telemetry. Society of

Neuroscience 28th Annual Mtg., Los Angeles, CA (1998).

BA Murphy, CN Nunes, AM Fairhurst, MJ Donnelley, and TN Mellin.SHU9119

Inhibits MTII, but not Dexfenfluramine Induced Anorexigenesis. Society of

Neuroscience 29th Annual Mtg., Miami, FLA (1999).

JN Stair, J Shu, R Camacho, BA Murphy, G Hickey, DE MacIntyre and AM

Strack. Feeding Behavior in Rats Chronically Treated with Melanocortin

Agonist, MTII. Society of Neuroscience 29th Annual Mtg., Miami, FLA (1999).

BA Murphy, G Hickey and AM Strack. Effect of peripheral melanocortins, MTII

and SHU9119, on LPS fever in rats. Society of Neuroscience 30th Annual

Mtg., New Orleans, LA (2000).

JN Gorski, BA Murphy, GJ Hickey, AM Strack, and J Metzger. Comparison of

CNS infusion of melanocortin nonselective and -4 receptor selective

agonists on energy balance in rats. Annual Meeting of the Society for the

Study of Ingestive Behavior, Santa Cruz, California (2002).

BA Murphy and BA Rocha. Gender differences the tail suspension test (TST)

among C57BL/6N and 129/SV inbred mice. Society for Neuroscience 32nd Annual

Meeting, Orlando, Florida (2002).

BA Murphy, C Abbadie, GJ Kaczorowski, JA Lindia, BT Priest, AM Ritter, WJ

Martin. Contribution of the tetrodotoxin-resistant sodium channel nav1.9 to

sensory transmission and nociceptive behavior in mouse. For presentation

at: Society for Neuroscience 34th Annual Meeting, San Diego, California

(2004)

WJ Martin, A Ritter, K Parsons, BA Murphy, J Parsons, S Cupo, S-L Chen, D

Zaller, I-M Wang, SJ O'Keefe. p38? contributes to injur-induced

nociceptive, but not inflammatory, responses in mice. For presentation at:

Society for Neuroscience 35th Annual Meeting, Washington DC (2005).

BA Murphy, N Jochnowitz, AM Strack, WJ Martin. Melanocortin receptor

activation regulates the release of NPY from rat hypothalamus in vitro.

For presentation at the Experimental Biology Meeting, San Francisco (2006).

BA Murphy, K Gagen, N Jochnowitz, AM Strack, VH Routh. Glucose regulates

feeding-state dependent NPY release from rat hypothalamus in vitro. For

presentation at Society for Neuroscience 37th Annual Meeting, San Diego

(2007).

PUBLICATIONS:

Theodore N. Mellin, Doreen Cashen, John J. Ronan, Beth A. Murphy, Jerry

DiSalvo, and Kenneth A. Thomas. Acidic Fibroblastic Growth Factor

Accelerates Dermal Wound Healing in Diabetic Mice. J of Invest Dermatology

104: 850-55, 1995.

B Murphy, CN Nunes, JJ Ronan, CM Harper, MJ Beall, MJ Hanaway, AM

Fairhurst, LHT Van Der Ploeg, DE MacIntyre and TN Mellin. Melanocortin

Mediated Inhibition of Feeding Behavior in Rats. Neuropeptides, 1998:32

(6), 491-497.

JP Varnerin, T Smith, CI Rosenblum, A Vongs, B Murphy, C Nunes, TN Mellin,

JJ King, BW Burgess, B Junker, M Chou, P Hey, E Frazier, LHT Van der Ploeg

and MR Tota. Production of leptin in E. Coli: A comparison of Methods.

Protein Expression and Purification. 1998:13(3), 335-42.

KM Bullard, L Lund, JS Mudgett, Z Werb, TN Mellin, TK Hunt, B Murphy, J

Ronan and MJ Banda. Impaired Wound Contraction in Stromelysin-1 Deficient

Mice. Annals of Surgery, 1999: 230 (2), 260-5.

B Murphy, CN Nunes, JJ Ronan, M Hanaway, AM Fairhurst, TN Mellin. Centrally

administered MTII affects feeding, drinking, temperature and activity in

the Sprague-Dawley rat. J Appl Physiol, 2000: 89, 273-282.

AD Howard, R Wang, S Pong, TN Mellin, A Strack, X-M Guan, Z Zeng, DL

Williams, SD Feighner, CN Nunes, B Murphy, JN Stair, H Yu, Q Jiang, MK

Clements, CP Tan, KK McKee, DL Hreniuk, TP McDonald, KR Lunch, JF Evans, CP

Austin, T Caskey, LHT Van der Ploeg, Q Liu. Identification of receptors for

neuromedin U and its role in feeding. Nature, 2000:406, 70-74.

AM Strack, J Shu, R Camacho, JN Gorski, B Murphy, DE MacIntyre and GJ

Hickey. Regulation of body weight and carcass composition by sibutramine in

rats of differing adiposities and age. Obesity Research, 2000:10(3): 173-

181.

Priest BT, Murphy BA, Lindia JA, Diaz C, Abbadie C, Ritter AM, Liberator P,

Iyer LM, Kash SF, Kohler MG, Kaczorowski GJ, MacIntyre DE, Martin WJ.

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel

NaV1.9 to sensory transmission and nociceptive behavior. PNAS, 2005:

(102):26,9382-7.

B A Murphy, X Fioramonti, N Jochnowitz, K Fakira,K Gagen, S Contie, A

Lorsignol, Luc Penicaud, WJ Martin and VH Routh. Fasting enhances the

response of arcuate neuropeptide Y (NPY)-glucose-inhibited (GI) neurons to

decreased extracellular glucose. American Journal of Physiology - Cell

Physiology 2009 Sep; Apr;296(4):C746-56.

BA Murphy, KA Fakira, Z Song, A Beuve, VH Routh. AMP-activated protein

kinase and nitric oxide regulate the glucose sensitivity of ventromedial

hypothalamic glucose-inhibited neurons. American Journal of Physiology -

Cell Physiology 2009 Sep; Apr;297(3):C750-8.

Kevin J. Hodgetts,, Charles A. Blum, Timothy Caldwell, Rajagopal

Bakthavatchalam,, Xiaozhang Zheng, Scott Capitosti, James E. Krause,

Daniel Cortright, Marci Crandall, Beth Ann Murphy, Susan Boyce, A. Brian

Jones and Bertrand L. Chenard. Pyrido[2,3-b]pyrazines, discovery of TRPV1

antagonists with reduced potential for the formation of reactive

metabolites . Bioorgan Med Chem Letters. 2010 Aug; 20 (15):4359-63.

Blum CA, Caldwell T, Zheng X, Bakthavatchalam R, Capitosti S, Brielmann H,

De Lombaert S, Kershaw MT, Matson D, Krause JE, Cortright D, Crandall M,

Martin WJ, Murphy BA, Boyce S, Jones AB, Mason G, Rycroft W, Perrett H,

Conley R, Burnaby-Davies N, Chenard BL, Hodgetts KJ. Discovery of novel 6,6-

heterocycles as transient receptor potential vanilloid (TRPV1) antagonists.

J Med Chem. 2010 Apr 22;53(8):3330-48.

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