Department of Pharmacology Overview

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Department of PharmacologyOverview

• Heidi E. Hamm, Ph.D.
• Earl W. Sutherland, Jr. Professor of Pharmacology
• Chair, Department of Pharmacology

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Vanderbilt Pharmacology

• Pharmacology the study of how chemical agents
  affect living processes.
• Vanderbilt Pharmacology one of the most
  distinguished Pharmacology departments in the
  country
• Within the top two NIH ranking positions for
  sixteen of the last twenty years

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Five decades of Pharmacology at Vanderbilt
Joel G. Hardman, Ph.D., Pharmacology Chair
1974-1990
Lee E. Limbird, Ph.D., Pharmacology Chair
1991-1998
Elaine Sanders-Bush, Ph.D., Pharmacology Chair
1999- 2000
Heidi E. Hamm, Ph.D., Pharmacology Chair 2000 -
Present
Allan D. Bass, M.D., Pharmacology Chair 1953-1973
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Alan Bass Recruited John Oates

• Professor of Pharmacology
• Founded Division of Clinical Pharmacology, Chief,
  1963-1988
• Chair of Medicine, 1983-1997
• Research area lipid mediators
• Alzheimers disease

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Joel Hardman recruited Lee Limbird

• Molecular pharmacology focus
• Signal Transduction
• G protein-coupled
• receptors
• gt3 of the human genome
• most successful drug targets
• more specific therapies
• with less side effects?

Hormone
Receptor
G protein
GDP
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Signal Transduction Research Themes

• Receptors, G-proteins and trans-membrane
  signaling within and between cells via electrical
  and chemical messages
• Molecules under investigation
• G-protein coupled receptors (rhodopsin,
  adrenergic, serotonin, thrombin,
• glutamate, LPA, purinergic receptors)
• Heterotrimeric G proteins, small G proteins
• Ion channels
• Transporters
• Regulatory proteins such as arrestins,
  scaffolding proteins,
• Protein kinases, protein phosphatases,
  phospholipases
• Lee Limbird, Elaine Sanders-Bush, Jeff Conn,
  Heidi Hamm, John Exton, Alex Brown, Seva
  Gurevich, Rich Breyer, Terry Lybrand, Joey
  Barnett, others

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Department of Pharmacology

• Signal transduction
• Lee Limbird, Elaine Sanders-Bush, Jeff Conn,
  Heidi Hamm, John Exton,
• Seva Gurevich, Rich Breyer, Terry Lybrand, Joey
  Barnett, others
• Synaptic transmission and neuroscience
• Randy Blakely, Lou Defelice, Ron Emeson, Jeff
  Conn, Elaine Sanders-Bush, others
• Biosynthesis and metabolism of metabolites
  of arachidonic acid
• John Oates, Jack Roberts, Jason
  Morrow, Alan Brash, Alex Brown, others
• Electrical and genetic basis of
  cardiovascular diseases
• Dan Roden, Jeff Balser, Al George, Mark
  Anderson, Kathy Murray, others
• Drug metabolism and inter-patient
  variability in therapeutic
• response
• Grant Wilkinson, Richard Kim,
  Alistair Wood, Dan Roden, others

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Major investment in Pharmacology

• Doubling the size of the Department
• (from 13 to 26)
• 8 new faculty members 2000-2004
• Expansion of space
• New research directions

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Pharmacology Current and Future Directions
PHARMACOLOGY
Neuroscience Blakely DeFelice Emeson Levitt Gurevi
ch McDonald Shieh
Drug Discovery Conn Forster Niswender (future
searches)
Clinical Pharmacology Wilkinson Roberts Brash Rode
n Morrow Oates Tirona
Structural Biology Tina Iverson (current
search)
Systems Biology Chung Peterson (future
searches)
Receptors Signal Transduction Hamm Sanders-Bush
Conn Gurevich Limbird Brown Barnett Wadzinski
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Arrestin structure and function
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Chemotaxis
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Lipid signal transduction
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Developmental neurobiology
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Small molecule discovery
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Dopamine receptors
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Ribosome display libraries
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Recruitment, 2000-2004
Successful recruitments

• 2001 Seva Gurevich
• Chang Chung
• 2002 Alex Brown
• Pat Levitt
• 2003 Jeff Conn
• Eugenia Gurevich
• 2004 Tony Forster
• Tina Iverson

Membrane protein crystallography
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Pharmacology Development

• Build on strengths in signal transduction and
  
• clinical pharmacology

1. Lipid signaling
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Alex Brown, Lipidomics

• Ingram Associate Professor of Cancer Research
• Joint recruit between Pharmacology and Chemical
  Biology
• Receptor-mediated regulation of phospholipase D

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Pharmacology Development

• Build on strength in signal transduction and
• clinical pharmacology

• Lipid signaling
• Structural biology
• Systems biology
• Drug discovery

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Systems biology

• A systems level characterization of a biological
  process
• 1) What are the parts of the system (i.e., the
  genes and the proteins they encode)?
• 2) How do the parts work?
• 3) How does the ensemble accomplish a task?
• Systems biology seeks to predict biological
  phenomena using mathematical modeling and
  simulation.
• Pharmacology focus predict better targets for
  drug discovery, predict drug responses

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P. Jeffrey Conn

• Head of Neuroscience,
• Merck Res. Inst.
• Professor, Department of Pharmacology
• Director of the VICB Program in Drug Discovery
• Novel therapeutic approaches for treatment of
  Parkinsons disease.

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Pharmacology a triple threat

• Top ranked in scientific citations
• Top ranked in NIH funding
• Top ranked in graduate training program

Joey Barnett, Director of Graduate Studies
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Impact of Publications Pharmacology
ISIs University Science Indicators
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Historical NIH Ranking (in dollars awarded)
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Administrative Staff Organizational Chart
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Administrative Staff in Pharmacology-Who Are They?

• Departmental Administrator-
• Connie Stenquist
• Administrative Officer-
• Pamela Harrell

• HR Manager-
• Sharon Sumrell

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Administrative Staff in Pharmacology-Who Are They?

• Purchasing/Move Coordinator-
• Yvonne Smith
• Executive Secretary -
• Tina Mead

• Grants Manager-
• Paige Robinson
• Graduate Program Coordinator-
• Karen Gieg

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Administrative Staff in Pharmacology-Who Are They?

• Manager, Chairs Office -
• Elaine Brown
• Educational Coordinator
• Chairs Office-
• Chase Jeffords

• LAN Manager -
• Gordon Borck
• Sr. Executive Secretary -
• Donna Ingram

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Administrative Staff headcount is stable
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Significant growth in researchers matches the
growth in research funding
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Departmental Mission Statement

• We engage in scientific discovery to elucidate
  biological mechanisms and develop novel
  therapeutics. We provide training focused on
  critical thinking to promote innovation,
  scholarship and integrity. To this end, we foster
  creativity, collegiality, and leadership.

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Equipment Needs

• The Department has some core equipment.
• A significant amount of equipment is purchased by
  individual faculty/labs.
• The Department often pays service contracts on
  equipment owned by individual faculty.
• Future core equipment needs.
• Faculty to determine areas of need
• Pooled resources from several investigators plus
  departmental help to purchase equipment?

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Departmental Equipment

• Tissue culture room with hoods and incubators
• Dark Room and film processor (5th floor)
• Spectrophotometers, Fluorometers
• Fluorescence and visible 96-well plate readers
• Light and fluorescence microscopes (Nikon, Zeiss,
  deconvolution)
• FLEX stations (2)
• Single cell Ca imaging system
• Centrifuges 4 Sorvalls, 2 ultracentrifuges and
  rotors
• Gel documentation Bio-Rad Fluor-S, Odessy,
  transilluminator
• Lyophilizer, SpeedVac
• Floor Shakers 5, for yeast, bacteria and SF9
  cells
• Incubators for yeast, bacteria
• Ice machines
• Scintillation counters (3), Gamma counter
• -80 degree Freezer

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Return on Investment
8 NIH funding for each 1 in development
spending 10 total funding for each in
development spending
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What are Pharmacologys Untapped or Partially
Tapped Opportunities?

• Cancer Pharmacology
• Pharmacology Drug Discovery
• Partnerships with Clinical Pharmacology
• drug disposition, cancer pharmacology
• Systems Biology
• What else?

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Pharmacology Current and Future Directions
PHARMACOLOGY
Neuroscience Blakely DeFelice Emeson McDonald Shi
eh Levitt Gurevich (current search)
Drug Discovery Conn Forster Brown (current
search)
Clinical Pharmacology Wilkinson Roberts Brash Rode
n Morrow Oates Kim Tirona Knollmann (current
searches)
Structural Biology Gurevich Tina Iverson Ben
Spiller Meiler
Systems Biology Chung Brown Hamm (current
search)
Receptors Signal Transduction Hamm Sanders-Bush
Limbird Barnett Wadzinski Gurevich Brown Conn (cu
rrent search)
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Systems Biology

• A systems level characterization of a biological
  process
• 1) What are the parts of the system (i.e., the
  genes and the proteins they encode)?
• 2) How do the parts work?
• 3) How does the ensemble accomplish a task?
• Systems biology seeks to predict biological
  phenomena using mathematical modeling and
  simulation.
• Pharmacology focus predict better targets for
  drug discovery, predict drug responses

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Research Focus for Vanderbilt Medical Center Over
the Next Five Years

• Personalized Medicine Individualizing care
  through understanding how an individual's
  molecular, economic and social context predicts
  risk of disease and response to therapy.
• Therapeutic Discovery and Translation To
  discover new therapies and therapeutic targets,
  and accelerate their translation to clinical
  practice.
• Population Health Care To understand how best
  to deliver the highest quality health care to
  diverse populations.

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Department of PharmacologyTraining Program

• Joey V. Barnett, Ph.D.
• Associate Professor of Pharmacology
• Director of Graduate Studies

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What are our Goals?
Provide expertise in the principles of
pharmacology
Direction to define and solve problems in a
specific area
Free trainees from a fear of failure
Develop scientists who make significant
contributions
Our overall goal is to train scientists who will
be leaders in academia, industry, or regulatory
affairs.
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Who are our students?
Total 47 males/females 23/24 Underrepresented
minorities 4 Non U.S. citizens 10 Medical
Scientist Training Program 9 Average
G.P.A./G.R.E. 3.5/1950
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How successful are we?
National Academy of Sciences
Ranked number 3 based on program effectiveness
in educating research scholars and scientists.
Only preceded by Yale University in the number of
respondents who ranked our Program as
Distinguished or Strong.
Rank of 6 with respect to the scholarly quality
of program.
Funded by the NIH since 1958.
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Summary of Graduate Fates
Total of 150 Ph.D.s Awarded since 1934
Academia 55 Industry 29 Institutes 5 Postdo
ctoral Fellows 30
Our Graduates are highly sought after by Industry
and Academia
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Other Training Opportunities

• Undergraduate Program
• PharmX
• Outreach
• Postdoctoral Training
• Medical Students

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Department of PharmacologyClinical Pharmacology

• Jason D. Morrow, M.D.
• Professor, Departments of Pharmacology and
  Medicine
• Incoming Chief, Division of Clinical Pharmacology

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Division of Clinical Pharmacology

• Division is a component of both Departments of
  Pharmacology and Medicine.
• Founded 1963 by John Oates and Allan Bass.
• Mission - Understanding mechanisms of drug action
  in humans in order to improve therapeutics.
• Focus is on basic and translational research.
• Integrates with other efforts in the
  pharmacological sciences - VICB and Pharmacology
  Drug Discovery.

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Division of Clinical Pharmacology

• Areas of research focus
• Drug disposition and metabolism in humans
• Faculty - Wilkinson, Roden, Wood, Kim
• Fatty acid oxidation and lipid mediators
• Faculty - Morrow, Brash, Roberts, Oates
• Ion channel biology and arrhythmia
  pharmacogenomics
• Faculty - Roden, Kim, Murray
• Human cardiovascular pharmacology and neural
  dysfunction
• Faculty - Robertson, Wood, Stein, Murphey,
  Biaggioni, Raj, Gainer, Brown.

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Division of Clinical Pharmacology

• Largest and most successful division of its kind
  in the world.
• 32 faculty-15 tenure track, 17 research track.
• 24 fellows currently in program.
• 330 fellows trained since 1963 many in
  leadership positions in academia and industry.
• Division faculty lead most physician-scientist
  training programs at VUMC.
• 2004 NIH research awards gt20 million.
• 2004 77 peer-reviewed publications to date.
• Nature
• New England Journal of Medicine
• Proceedings of the National Academy of Sciences
  USA
• Journal of Clinical Investigation

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The Future of Clinical Pharmacology at Vanderbilt

• Division is uniquely poised to capitalize on NIH
  Roadmap initiatives related to translational
  research.
• New Division Chief
• Jason D. Morrow M.D., Billings Professor of
  Pharmacology and Medicine
• 7-8 new faculty recruits into areas of research
  strength.
• Oates Chair in Translational Research
• Oates Institute of Experimental Therapeutics.
• Goal is to expand Clinical Pharmacology to the
  university as a whole and establish an
  institution-wide program in this area of
  investigation.
• Director - Dan M. Roden M.D., Stokes Professor of
  Pharmacology and Medicine.
• To be housed in MRB-IV (11,000 square feet).

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VICB Program in Drug Discovery

• P. Jeffrey Conn
• Department of Pharmacology

Mission to promote translation of advances in
basic science to novel therapeutics and
marketable products.

• Develop small molecules and biological reagents
  that allow proof-of-concept studies that lead to
  new approaches for development of therapeutic
  agents
• Develop key reagents for the scientific
  community to spur further research in these areas
  that could lead to innovative approaches to
  therapeutics.

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VICB Program in Drug Discovery
External Collaborators ChemDiv, ChemBridge
Chemical Synthesis core
HTS Facility
Department of Pharmacology
Clinical Pharmacology Division
Small Molecule NMR Facility
Vanderbilt Ingram Cancer Center
Vanderbilt Mass Spec Research Center
General Clinical Research Center
Murine Bio-behavioral Core
Vanderbilt Brain Institute
Vanderbilt Imaging Research Center
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Neuroscience Research Themes

• Neural Signaling and the Actions of
  Psychoactive Drugs
• Genetic Models of Behavioral and
  Neurodegenerative Disorders
• Human Neuropharmacology and Genetic Determinants

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Center for Molecular Neuroscience

• Initiated through Dept. Pharmacology in 1996
• 54 Faculty from 11 Depts
• School of Medicine
• College of Arts and Sciences
• Infrastructure Support for Research and Training
  in Molecular Neurobiology
• Home for Postdoctoral Neurogenomic Training
  Program

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CMN Core Facility Support

• Neurogenomics Detection of Genetic Variants in
  Human Neural Genes
• Neurochemistry Analysis of Neurotransmitters
  and Metabolites
• ES/Transgenic Core
• (R. Emeson, Ph.D. Director)
• Production of Genetically Altered Mice
• Neurobehavior Core
• (M. McDonald,Ph.D. Director)
• Behavioral Analysis of Transgenic Mice
• Cellular Neuroimaging
• Widefield and Confocal Imaging of Neural Cells

MRBIII Home to Blakely, Emeson, Sanders-Bush,
DeFelice, Levitt
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Leadership in Campus Neuroscience