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Peter S. Klein, MD, PhD Physician

Director, Physician-Scientist Program Professor of Medicine Professor of Cell and Developmental Biology

Dr. Klein is employed by Penn Medicine.

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Clinical Specialties


  • Hematology

Programs & Centers:

Board Certification:

  • Hematology, 2008

Clinical Expertise:

  • Acute Lymphocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Promyelocytic Leukemia
  • Adult T-Cell Leukemia
  • Adult T-Cell Lymphoma
  • AIDS Related Malignancies
  • Amyloidosis
  • Anaplastic Large Cell Lymphoma
  • Bone Marrow Biopsy
  • Bone Marrow Failure Syndromes
  • Burkitt Lymphoma
  • Cancer During Pregnancy
  • Castleman Disease
  • Chronic Lymphocytic Leukemia
  • Chronic Myelocytic Leukemia
  • Chronic Myelomonocytic Leukemia
  • CNS Lymphoma
  • Cutaneous Lymphoma
  • Eosinophilic Granuloma
  • Erdheim-Chester Disease
  • Essential Thrombocytosis
  • Graft Versus Host Disease
  • Hairy Cell Leukemia
  • Hematologic Malignancies
  • Histiocytosis
  • HIV Lymphoma
  • HIV Malignancies
  • Hodgkin Lymphoma
  • Intraocular Lymphoma
  • Large Granular Lymphocytic Leukemia
  • Leukemia
  • Light Chain Disorders
  • Lymphoma
  • Marginal Zone Lymphoma
  • Mediastinal Lymphoma
  • Monoclonal Gammopathy of Undetermined Significance
  • Mucosa-Associated Lymphoid Tissue Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes (MDS)
  • Myeloproliferative Neoplasms (MPN)
  • Non-Hodgkin Lymphoma
  • Pelvic Malignancy During Pregnancy
  • Peripheral T-Cell Lymphoma
  • Plasma Cell Dyscrasia
  • POEMS Syndrome
  • Polycythemia
  • Primary Myelofibrosis
  • Prolymphocytic Leukemia
  • Refractory Anemia With Excess Blasts
  • Sezary Syndrome
  • Transformed Lymphoma
  • Waldenstrom Macroglobulinemia (WM)
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Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Amerihealth Caritas
  • Amerihealth Caritas Medicare
  • Cigna
  • Cigna HealthSpring
  • Clover Health Plan
  • CVS Health
  • Devon Health Services (Americare)
  • eLAP Services
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Homestead Smart Health Plans
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Keystone First Medicare
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oscar Health Plan of PA
  • Oxford Health Plan
  • PA Health and Wellness (Centene) Medicare
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Provider Partners Health Plan
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan
  • Veterans Choice Program

Education and Training

Medical School: Johns Hopkins University School of Medicine
Residency: Massachusetts General Hospital
Fellowship: Harvard Medical School


American Association for the Advancement of Science, National American Society for Clinical Investigation, National American Society for Microbiology, National American Society of Hematology, National Association of American Physicians, National National Institutes of Health, National NHLBI, NIH, R38 StARR study section, National Society for Developmental Biology, International

Hospital Affiliation

Dr. Klein is employed by Penn Medicine.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.


Description of Research Expertise:

Research Interests
Early vertebrate development and pattern formation, Wnt signaling, chromatin and epigenetic regulation of early development, hematopoietic stem cell biology, neural stem cells and neurogenesis, neuropharmacology of bipolar disorder, lithium and glycogen synthase kinase-3 (GSK-3).

Key words: Wnt, embryo, signaling, signal transduction, developmental biology, lithium, chromatin, epigenetic, hematopoiesis, stem cell, GSK-3, mTOR, behavior, affective disorders.

Description of Research
This lab studies patterning in early vertebrate development, the regulation of stem cell self-renewal in the hematopoietic system, adult neurogenesis, Wnt signaling, and the molecular mechanisms in the pathogenesis and treatment of neuropsychiatric disorders. Areas of current research include:

1) Wnt signaling modifies chromatin architecture to control early development: We have found that Wnt signaling through ß-catenin establishes poised chromatin architecture at Wnt target promoters in the early embryo. We have identified Prmt2 as a histone H3 arginine-8 methyltransferase and shown that it is recruited by ß-catenin to Wnt target gene promoters and is required for dorsal-ventral patterning. We are currently examining the requirement for Prmt2 in other Wnt-regulated contexts in development and in somatic stem cell populations. We are also exploring the regulation of zygotic gene expression before the midblastula transition, focusing on the role of preMBT transcription in germ layer specification. These experiments are being carried out in Xenopus laevis embryos and in mouse hematopoietic stem cells, and involve microinjection, microsurgical procedures, molecular analysis of chromatin structure and gene expression, and biochemical analysis of the Wnt signaling pathway.

2) Wnt and GSK-3 regulation of hematopoietic stem cell (HSC) self-renewal: We are studying the roles of GSK-3 and Wnt signaling in HSC homeostasis in vivo and in primary HSC culture. We are exploring novel ex vivo culture techniques to define the signaling pathways required for and the gene expression profile associated with HSC self-renewal. In collaboration with Wei Tong at CHOP, we are also studying how JAK/STAT signaling interacts with GSK-3 and Wnts to regulate HSC renewal. These experiments are being carried out with mouse and human hematopoietic stem cells, using novel ex vivo culture techniques and stem cell transplantation assays in mice. These experiments also involve flow cytometry and cell sorting, RNA interference, and biochemical analysis of transmembrane signaling pathways. Our long-term interest is to adapt these findings to clinical applications including hematopoietic stem cell transplantation in humans and treatment of bone marrow failure disorders.

3) Neural signaling pathways that mediate the response to mood stabilizing drugs, with a focus on lithium, GSK-3, and Wnt signaling in the adult central nervous system, in order to understand the molecular pathogenesis and pharmacotherapy of bipolar disorder. This laboratory identified GSK-3 as a direct target of lithium, the most widely used and effective treatment for bipolar disorder. We are currently investigating the downstream molecular targets and the neuronal cell populations within the brain that mediate the response to mood stabilizing drugs. For these experiments, we use neural specific gene knockout and transgenic mice, multiple behavioral assays in adult mice, and in vivo analysis of neural stem cell proliferation and differentiation. In collaboration with Celeste Simon, we are examining interaction between hypoxia inducible factors, GSK-3, and the Wnt pathway in regulating neuronal stem/progenitor cells and the potential role of this cell population in mood disorders.

4) Molecular mechanisms of Wnt signaling: We are also investigating the molecular mechanisms of Wnt signaling, with a focus on how GSK-3 activity is regulated by Wnts. We have found that GSK-3 is positively regulated by the tumor suppressor APC. We are exploring the hypothesis that APC regulates multiple targets through the regulation of GSK-3 activity.

Rotation Projects
1. Molecular analysis of hematopoietic stem cell signaling in vivo and in ex vivo culture.

2. Chromatin modifications in response to Wnt signaling in HSCs.

3. PreMBT regulation of dorsal-ventral patterning and Wnt signaling in Xenopus embryos.

4. Chromatin modifications in response to developmental signals.

5. Signaling through APC and GSK-3 in colon cancers and other neoplastic syndromes.

6. Mechanisms of lithium action in model systems.

Lab personnel:
Dheeraj Bhavanasi, postdoctoral fellow
Mindy Snitow, postdoctoral fellow
Michelle Nguyen-McCarty, graduate student
Mansi Shinde, graduate student
Kelsey Speer, graduate student (Lemmon and Klein labs)
Melody Esmaeili, graduate student
Rebecca Myers, graduate student
Yuchen Wang, visiting graduate student
Pamela Burgess-Jones, lab manager
Amanda Reichert, research specialist
Jian Huang, visiting scientist

Selected Publications:

Valvezan AJ, Huang J, Lengner CJ, Pack M, and PS Klein: Oncogenic mutations in Adenomatous Polyposis Coli (Apc) activate mechanistic Target of Rapamycin Complex 1 (mTORC1) Disease Models and Mechanisms 7 (1): 63-71,2014.

Huang J, Nguyen-McCarty M, Hexner EO, Danet-Desnoyers G, and PS Klein: Maintenance of Hematopoietic Stem Cells through regulation of Wnt and mTOR Pathways Nature Medicine 18 : 1778-1785,2012.

Valvezan AJ, Zhang FS, Diehl JA, and PS Klein: Adenomatous Polyposis Coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity Journal of Biological Chemistry 287 : 3823-3832,2012.

Skirkanich J, Luxardi G, Yang J, Kodjabachian L, and PS Klein: An essential role for transcription before the MBT in Xenopus laevis. Developmental Biology 357 : 478-491,2011.

O’Brien WT, Huang J, Buccafusca R, Garskof J, Valvezan AJ, Berry GT, and PS Klein: Glycogen synthase kinase-3 is essential for β-arrestin-2 complex formation and lithium-sensitive behaviors in mice. Journal of Clinical Investigation 121 : 3756-3762,2011.

Blythe SA and Klein PS: Prepatterning embryonic development: tabula scripta? Developmental Cell 21 : 977-978,2011.

Blythe SA, Cha SW, Tadjuidje E, Heasman J, Klein PS: beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2. Developmental Cell 19 (2): 220-231,2010.

Mazumdar J, O'Brien WT, Johnson RS, LaManna JC, Chavez JC, Klein PS, Simon MC: O2 regulates stem cells through Wnt/β-catenin signalling. Nature Cell Biology 12 (10): 1007-13,2010.

Huang J, Zhang Y, Bersenev A, O'Brien WT, Tong W, Emerson SG, Klein PS: Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice. Journal of Clinical Investigation 119 (12): 3519-29,2009.

View all publications

Academic Contact Info

9-103 Smilow Center for Translational Research (SCTR)
Perelman School of Medicine at the University of Pennsylvania
3400 Civic Center Blvd.

Philadelphia, PA 19104-5157
Phone: (215) 573-2931
Patient appointments: 800-789-7366 (PENN)

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