B.S. Biochemistry, University of Illinois (Urbana-Champaign)
Ph.D.(Pharmacology-Toxicology), University of
Arizona
Postdoctoral Fellow, Northwestern University Medical
School
Courses Taught (Undergraduate)
- Human Physiology
- Pathology I and II.
Focus is on cell biology, endocrinology and reproduction.
- Biomedical Sciences
- Therapeutics.
Focus is on the pathophysiology
and pharmacology of endocrine disorders.
(Graduate)
- Course Master: Mechanisms
of Drug Action.
Focus is on receptors, G-proteins
and various signaling pathways involved in cellular
processes.
- Methods of Evaluation
of Drug Action and Toxicity.
Focus is on ethics
associated with research, proper laboratory procedures
and calculations, radioligand binding analysis,
and protein analysis.
Areas of Research
- Molecular mechanisms underlying melatonin receptor
function
- Development of melatonin receptor ligands
- Modulators of G-protein function, including the
role of GAPs and microtubules
- Role of melatonin receptors in breast cancer
- Role of melatonin receptors in human adult mesenchymal
stem cell differentiation into osteoblasts.
SCIENCE FEATURES
Invited Reviews
- Grant, S.G., Melan, M.A., Latimer, J.J., and Witt-Enderby, P.A..Melatonin and Breast Cancer: Cellular Mechanisms, Clinical Studies and Future Perspectives In Expert Reviews in Molecular Medicine, 11: E5, 2009.
- Witt-Enderby, P.A., Radio, N.M., Doctor, J.S., and Davis, V.L.. MINIREVIEW
Therapeutic Treatments Potentially Mediated by Melatonin Receptors: Potential Clinical Uses in the Prevention of Osteoporosis, Cancer and as an Adjuvant Therapy. In Journal of Pineal Research 41 (4):297- 305, 2006.
- Witt-Enderby, P.A., Bennett, J., Jarzynka, M.J.,
Firestine, S. and Melan, M.A. Melatonin Receptors
and their Regulation: Biochemical and Structural
Mechanisms In Life Sciences, 72(2): 2183-2198
(2003).
- Witt-Enderby, P.A. and Li, P.K, Melatonin Receptors
and Ligands InVitamins and Hormones 58: 321-354
(2000).
- Li, P.K. and Witt-Enderby, P.A., Melatonin Receptors
as Targets for Drug Discovery, In Drugs of the
Future, 25(9): 945-957 (2000).
Grant Support
- 01/01/08-12/31/11, "The Effect of Melatonin on Bone Turnover Markers in Peri-menopausal Women", Translational Research Grant, Duquesne University. PI. $20,000.
- 01/01/08-12/31/10, "Development of a Bone-Regenerative Scaffold," Pennsylvania Department of Health, $42,274, PI.
- 05/01/07-04/30/08, "Pharmacological Evaluation of 13a, 14 dihydro-6H-pyrazino[1,2-a;4,5-a']diindole Analogs as Melatonin Receptor Ligands Using Competition Binding Analysis and Recombinant Cell Lines Expressing the Human MT1 and MT2 Melatonin Receptors" American Foundation for Pharmaceutical Education, "5000. This was a scholarship that my pharmacy student, Justin Julius, was awarded to work on a research project in my lab.
- 07/01/06-04/30/09, "The Effect of Melatonin's Efficacy at Reducing Primary and Metastatic Breast Cancer Risk", Susan G. Komen Breast Cancer Foundation $250,000, PI.
- 09/01/04-08/31/06, "Elucidating the Role that Melatonin and Its Receptors Play in the Differentiation of Human Adult Mesenchymal Stem Cells into Osteoblasts", American Foundation for Pharmaceutical Education, $12,000 . This was a scholarship that my doctoral student, Nick Radio, was awarded to supplement his stipend for the year.
- 02/01/04-01/31/05, "Structural Motifs Underlying G protein-coupled Receptor Function", Pennsylvania Health Assessment Fund, $29,000 (Collaborating Investigator, $13,000).
- 05/01/03-04/30/02, "Acquisition of a Confocal Microscope", National Science Foundation, $185,890 (Participating Member).
- 01/01/02-12/31/03, "Characterization of Melatonin's Role in Differentiating Human Osteoblasts", Pennsylvania Health Research Formula Fund $34,193.
- 06/01/02 - 05/31/03, "The Effect of Microtubule Depolymerization in the SCN of the Hypothalamus on the Entrainment of Circadian Rhythms in the Free-running Rat", Faculty Development Fund, Duquesne, University $10,000.
- 08/01/00-12/31/03, #R15NS38873 "Development of Melatonin Receptor Ligands", National Institute of Neurological Disorders and Stroke, Academic Research Enhancement Award $25,000 (Collaborating Investigator).
- 04/23/99-03/31/02, #R15DK54070 "Mechanisms Underlying Melatonin Receptor Function", National Institute of Diabetes and Digestive and Kidney Diseases, Academic Research Enhancement Award $92,613.
Recent Presentations
- "The Effects of and Mechanisms Underlying Melatonin-induced Cellular Differentiation", February 22, 2008, Department of Biology, Duquesne University, Pittsburgh, PA.
- "Melatonin Signaling and Cellular Differentiation: potential targets for the prevention of osteoporosis and breast cancer", August 10-15, 2008, Melatonin Receptors and Therapeutics, FASEB Summer Research Conference, Snowmass, CO.
- Witt-Enderby, P.A., Julius, J, Attia, M.I., and Zlotos, D.P. The Pharmacological Evaluation of Novel and High-Affinity Melatonin Receptor Ligands. Experimental Biology Abstract # 724.9, 2008.
- Sethi, S. and Witt-Enderby, P.A. Critical Time Periods of Melatonin Exposure Enhance Osteoblast Differentiation From Human Mesenchymal Stem Cells. Experimental Biology, Abstract # 782.12, 2008.
- Witt-Enderby, P.A., and Latimer, J.J. Melatonin Effects on Disease-free and Stage III Breast Tumor Cultures. University of Pittsburgh Cancer Institute Scientific Retreat, June 21-22, 2007.
- Kirker, R.M., Rea, S.L., Witt-Enderby, P.A., and Davis, V.L. Identification of Estrogen-Regulated Genes in the Lens Using ERd3 Transgenic Mouse Model with Inducible Cataracts. US-Japan Cooperative Cataract Research Group Meeting, Kailua-Kona, HI, Dec 2007.
- "Melatonin Effects on Cellular Differentiation: the potential involvement of stem cells", May 29, 2007, University of Pittsburgh, Center for Environmental Oncology, Pittsburgh, PA.
- "The Pharmacology of Pain Management", November 9, 2006, Ohio Hospice and Palliative Care Organization Conference, Columbus, OH.
"Panel Presentation on Proposal for Blackboard User Group" March 5, 2007, Pittsburgh Blackboard Users Conference, Duquesne University.
- Sethi, S., Radio, N, Jockers, R., Adams, W. and Witt-Enderby, P.A. Scaffolds Between MT2 Melatonin Receptors, Gi, Beta Arrestin, MEK and ERK Form in Differentiating Bone Stem Cells and These Processes Require Internalization; domains found to exist in the C-tail of the MT2 receptor. Experimental Biology, 2007.
- Invited Speaker, "Signaling Mechansims Underlying Melatonin-induced Cellular Differentiation", 2006 Melatonin Receptor Symposium, University of Illinois, Chicago, IL, September 29, 2006.
- "The Pharmacology of Pain Management with an Emphasis on Neuropathic Pain", July 15, 2006, HospiceCare 2020 Conference, ProCare/Hospice Care, Atlanta, GA.
- "Signaling Mechanisms Underlying Melatonin's Effects on Cellular Differentiation", June 15, 2006, Center for Environmental Oncology, University of Pittsburgh, Oakland, PA.
- "Use of Personal Response System (PRS) Keypads in the Classroom", Turning Point Technologies Symposium, March, 2006, Duquesne University
- Sethi, S., Adams, W. and Witt-Enderby, P.A. The Effect of C-terminal Tail Mutations on the Function and Internalization Patterns of MT1 and MT2 Melatonin Receptors Expressed in COS-7 Cells. Experimental Biology, Abstract # 172.1, 2006.
- Radio, N., Doctor, J., Jockers, R., and Witt-Enderby, P.A. MT2 Melatonin Receptors Couple to Gi Protein, Beta Arrestin and MEK/ERK (1/2) in an Agonist-dependent Manner in Human Adult Mesenchymal Stem Cells Differentiated into Osteoblasts. Experimental Biology, Abstract #172.4, 2006.
- Witt-Enderby, P.A., Bondi, C.D., and Melan, M.A.
MT1 Melatonin Receptors, EGF Receptors and Intact
Microtubules Modulate the Intracellular Translocation
Patterns of Activated MEK but not ERK in CHO
Cells Expressing the Human MT1 Melatonin Receptor.
Neuroscience Abstracts, Program no. 963.14.,
Abstract Viewer/Itinerary Planner, CD-ROM, 2004.
Radio, N.M, Doctor, J.S., and Witt-Enderby, P.A.
The Role of Melatonin, Melatonin Receptors and
MEK/ERK (1/2) in Differentiating Human Mesenchymal
Stem Cells into Osteoblasts. Neuroscience Abstracts,
Program no. 963.15, Abstract Viewer/Itinerary
Planner, CD-ROM, 2004.
- Konduru, N.V., Johnson, D.A., Fitz, N.F., Benloucif,
S., and Witt-Enderby, P.A. MT2 Melatonin Receptors
and MEK/ERK (1/2) Modulate Melatonin-Mediated
Phase Shifts of Circadian Activity Rhythms in
Long Evans Rats. Neuroscience Abstracts, Program
no. 195.10, Abstract Viewer/Itinerary Planner,
CD-ROM, 2004.
- Pokala, V.N., Fitz, N.F., Witt-Enderby, P.A.,
and Johnson, D.A. Septohippocampal Cholinergic
Lesion on Alpha Secretase Activity in Rat Hippocampus.
Neuroscience Abstracts, Program no. 846.14, Abstract
Viewer/Itinerary Planner, CD-ROM, 2004.
- Witt-Enderby, P.A. and Desselle, S.P. Evaluation
of a CD-ROM Tutorial Reinforcing Concepts in
Endocrinology, AACP Abstract, 2004.
- Desselle, S.P., Mattei, T.J., Adeyeye, C., Giannetti,
V.J., Harrold, M.W., O’Neil, C.K., Surratt,
C.K., and Witt-Enderby, P.A. Quantifying Units
of Production Among Pharmacy Academicians, AACP
Abstract, 2004.
- McFalls-Stringert., M.A., Mattei, T.J., and Witt-Enderby,
P.A. Center for Pharmacy Practice Exercises:
Integration, Reinforcement and the Enhancement
of Learning, AACP Abstract,2004.
Recent Publications
- Markl, C., Attia, M.I., Julius, J., Sethi, S., and Witt-Enderby, P.A.: Synthesis and
Pharmacological Evaluation of 1,2,3,4-tetrahydropyrazino [1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatonergic lignads. Bioorganic Medicinal Chemistry, 2009 (in press: doi: 10.1016/j.bmc.2009.04.068).
- Jarzynka, M.J., Passey, D.K., Johnson, D.A., Konduru, N., Fitz, N., Radio, N.M., Rasenick, M., Benloucif, S. and Witt-Enderby, P.A. Microtubules Modulate Melatonin Receptors Involved in Phase-shifting Circadian Activity Rhythms: In vitro and in vivo evidence, J Pineal Res, 46 (2): 161-171, 2009.
- Zlotos, D.P., Attia, M.I., Julius, J., Sethi, S. and Witt-Enderby, P.A.: 2-[(2,3-dihydro-1H-indol-1-yl)methyl]-melatonin Analogues: A novel class of MT2-selective melatonin receptor antagonists. J Med Chem, 52 (3): 826-833, 2009.
- Bondi, C.D., McKeon, R.M., Bennett, J.M., Ignatius, P.F., Brydon, L, Jockers, R., Melan, M.A., and Witt-Enderby, P.A.: MT1 melatonin receptor internalization underlies melatonin-induced morphologic changes in Chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1/2 and microtubule modulation. J Pineal Res 44 (3): 288-298, 2008.
- Attia, M.I. Witt-Enderby, P.A., and Julius, J.: Synthesis and pharmacological evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiindole derivatives as novel melatoninergic ligands. Bioorganic and Medicinal Chemistry, 16: 7654-7661, 2008.
- Sethi, S., Adams, W., Pollock, J. and Witt-Enderby, P.A.: C-terminal Domains within Human MT1 and MT2 Melatonin Receptors are Involved in Internalization Processes. J Pineal Res, 45 (2): 212-218, 2008.
- Attia, M.I., Julius, J., Witt-Enderby, P.A., and Zlotos, D.P.: Synthesis, NMR Conformational Analysis and Pharmacological Evaluation of 6,7, 13,14-tetrahydro-7aH-cyclobuta[2',3']indolo [2',1':2,3] pyrimido [1,2-a]indole analogs as potential melatonin receptor ligands, Organic and Biomolecular Chemistry, 5:2129-2137, 2007.
- Attia, M.I., Julius, J Witt-Enderby, P.A., and Zlotos, D.P.: Synthesis and Pharmacological Evaluation of 13a, 14-dihydro-6H, 13H-pyrazino[1,2-a;4,5-a']diindole analogs as potential melatonin receptor ligands, Tetrahedron, 63: 754-760, 2007.
- Jarzynka MJ., Passey D.K., Ignatius, P. F., Melan, M. A., Radio N. M., Jockers, R, Rasenick, M. M., Brydon, L. and Witt-Enderby. P. A. Modulation of Melatonin Receptors and G-protein Function by Microtubules Journal of Pineal Research 41: 324-336, 2006.
- Witt-Enderby, P.A., Radio, N.M., Doctor, J.S, and Davis, V.L.. MINIREVIEW. Therapeutic Treatments Potentially Mediated by Melatonin Receptors: Potential Clinical Uses in the Prevention of Osteoporosis, Cancer and as an Adjuvant Therapy In Journal of Pineal Research, 41: 297-305, 2006.
- Radio, N.M., Doctor, J.S., and Witt-Enderby, P.A.: Melatonin Enhances Alkaline Phosphatase Activity in Differentiating Human Adult Mesenchymal Stem Cells Grown in Osteogenic Medium via MT2 Melatonin Receptors and the MEK/ERK (1/2) Signaling Cascade, Journal of Pineal Research 40 (4):332-342, 2006.
- Surratt, C.K., Witt-Enderby, P.A., Johnson, D.A., Andersen, C.A., Bricker, J.D., Davis, V.L., Firestine, S.M., and Meng, W.M.: Development of a Neuroscience-oriented "Methods" Course for Graduate Students of Pharmacology and Toxicology. Cell Biology Education 5: 188-196, 2006.
- El-Sherif, Y., Witt-Enderby, P.A., Li, P.K.,
Tesoriero, J., Hogan, M.V., and Wieraszko, A.:
The Actions of A Charged Melatonin Receptor Ligand,
TMEPI, and an Irreversible MT2 Receptor Agonist,
BMNEP, on Mouse Hippocampal Evoked Potentials
in Vitro, Life Sciences 75: 3147-3156, 2004.
- Witt-Enderby, P.A. and McFalls-Stringert, M.A.:
The Integration of Basic Cell Biology Concepts
into the Practice of Pharmacy. American Journal
of Pharmaceutical Education [online serial] 68(2):
Article 40, 2004.
- Witt-Enderby, P.A., Krawitt, B.J., Jarzynka,
M.J., and Melan, M.A.: Knockdown of RGS4and b-tubulin
in CHO Cells Expressing the Human MT1 Melatonin
Receptor Prevents Melatonin-induced Receptor
Desensitization. Life Sciences 75: 2703-2715,
2004.
- Masana, M.I., Witt-Enderby, P.A. and Dubocovich,
M.L.: Melatonin Differentially Modulates the
Expression and Function of the hMT1 and hMT2
Melatonin Receptors Upon Prolonged Withdrawal.
Biochemical Pharmacology 65: 731-739, 2003.
- MacKenzie, R.S. , Melan, M.A., Deepshikha K.
Passey and Witt-Enderby, P.A.: Dual Coupling
of MT1 and MT2 Melatonin Receptors to Cyclic
AMP and Phosphoinositide Signal Transduction
Cascades and Their Regulation Following Melatonin
Exposure. Biochemical Pharmacology 63(4): 587-595,
2002.
- Chu, G-A., Witt-Enderby, P.A., Jones, M.P., and
Li, P-K.: Synthesis and Pharmacological Analysis
of High-Affinity Melatonin Receptor Ligands,
Chemical and Pharmaceutical Bulletin, 50(2):
272-275, 2002.
- Clemens, J.W., Jarzynka, M.J., and Witt-Enderby,
P.A., Down-regulation of mt1 melatonin receptors
in rat ovary following estrogen exposure, Life
Sciences 69(1): 27-35, 2001.
- Bordt, S.L, McKeon, R.M, Li, P.K., Witt-Enderby,
P.A., and Melan, M.A.: N1E115 Mouse Neuroblastoma
Cells Express mt1 Melatonin Receptors and Produce
Neurites in Response to Melatonin. Biochimica
et Biophysica Acta. 1499: 257-264, 2001.
- Jones, M.P., Melan, M.A. and Witt-Enderby, P.A.:
Melatonin Decreases Cell Proliferation and Transformation
in a Melatonin Receptor-Dependent Manner, Cancer
Letters, 151: 133-143, 2000.
- Witt-Enderby, P.A., MacKenzie, R.S., Carroll,
E.A., Bordt, S.L., and Melan, M.A. “Melatonin
Induction of Neurite-Like Structures in Non-neuronal
Cells that is Dependent on Expression of the
Human mt1 Melatonin Receptor. Cell Motility and
the Cytoskeleton, 46: 28-42, 2000.
- Witt-Enderby, P.A., Masana, M.I., and Dubocovich,
M.L.: Physiological Exposure to Melatonin Supersensitizes
the Cyclic Adenosine 3’,5’- Monophosphate-Dependent
Signal Transduction Cascade in Chinese Hamster
Ovary Cells Expressing the Human mt1 Melatonin
Receptor. Endocrinology, 139: 3064 - 3071, 1998.
- Li, P.K., Chu, G-H., Gillen, M.L, and Witt-Enderby,P.A.: Synthesis and Receptor Binding Studies
of Quinolinic Derivatives as Melatonin Receptor
Ligands. Bioorganic Medicinal Chemistry Letters,
7: 2177-2180, 1997.
- Li, P.K., Chu, G-H., Gillen, M.L., Parekh, T.,
and Witt-Enderby, P.A.: The Development of a
Charged Melatonin Receptor Ligand. Bioorganic
Medicinal Chemistry Letters, 7: 2409-2414, 1997.
- Witt-Enderby, P.A., Chu, G.H., Gillen, M.L.,
and Li, P.K.: The Development of a High-Affinity
Ligand that Binds Irreversibly to Mel1b Melatonin
Receptors. Journal of Medicinal Chemistry Letters,
Rapid Communication, 40: 4195-4198, 1997.
- Witt-Enderby, P.A. and Dubocovich, M.L.: Characterization
and Regulation of the Human ML1A Melatonin Receptor
in CHO Cells, Molecular Pharmacology, 50: 166-174,
1996
Professional Memberships
- President, Faculty Senate, Duquesne University (2006-2010)
- Acting President of the Faculty Senate, Duquesne
University (2004-2005)
- Vice President of the Faculty Senate, Duquesne
University (2004-2006)
- Society for Neuroscience
- American Society for Pharmacology
and Experimental Therapeutics
- Rho Chi Pharmacy Honor
Society
- American Association of
Colleges of Pharmacy (AACP)
- Faculty Advisor, Kappa
Epsilon (Alpha Phi Chapter),
- Professional Female
Fraternity
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