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Peter S. Klein, MD, PhD
Professor of Medicine
Department: Medicine
Graduate Group Affiliations
Contact information
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
Perelman School of Medicine at the University of Pennsylvania
3400 Civic Center Blvd.
Philadelphia, PA 19104-5157
Office: 215-898-2179
B.A. (Biochemistry)
Harvard College, 1980.
Ph.D. (Biological Chemistry)
Johns Hopkins University School of Medicine, 1988.
M.D. (Medicine)
Johns Hopkins University School of Medicine, 1988.
B.A. (Biochemistry)
Harvard College, 1980.
Ph.D. (Biological Chemistry)
Johns Hopkins University School of Medicine, 1988.
M.D. (Medicine)
Johns Hopkins University School of Medicine, 1988.
LinksPermanent link
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Pharmacological Sciences graduate group faculty webpage.
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Pharmacological Sciences graduate group faculty webpage.
Description of Research ExpertiseResearch Interests
Early vertebrate development and pattern formation, Wnt signaling, chromatin and epigenetic regulation of early development, hematopoietic stem cell biology, neuropharmacology of bipolar disorder, lithium and glycogen synthase kinase-3 (GSK-3).
Key words: Wnt, embryo, signal transduction, developmental biology, lithium, chromatin, epigenetic, hematopoiesis, stem cell, GSK-3, 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, 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) Neuronal 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 suppressed in response to Wnts and other upstream signals. We have found that GSK-3 is positively regulated by the tumor suppressor APC and are exploring the hypothesis that GSK-3 is functionally inhibited by dissociation of APC from GSK-3 containing complexes, such as the axin degradation complex.
Rotation Projects
1. Molecular analysis of hematopoietic stem cell signaling in vivo and in ex vivo culture.
2. Role of hypoxia in HSC maintenance and proliferation ex vivo.
3. Chromatin modifications in response to Wnt signaling in HSCs.
4. PreMBT regulation of dorsal-ventral patterning and Wnt signaling in Xenopus embryos.
5. Identify components of the Wnt regulated ß-catenin/Prmt2 complex.
6. Role of chromatin modifications in developmental plasticity and the response to developmental signals during early embryogenesis.
7. Use of microarray and RNA-seq to identify novel preMBT genes; characterization of function of genes expressed before MBT.
Lab personnel:
Dheeraj Bhavanasi, postdoctoral fellow
Michelle Nguyen-McCarty, graduate student
Mansi Shinde, graduate student
Kelsey Speer, graduate student (Lemmon and Klein labs)
Melody Esmaeili, graduate student
Matthew Dong, undergraduate
Jessica Manlove, lab manager
Jian Huang, visiting scientist
Alexandra Bersani, graduate student (Master's)
Selected PublicationsHuang 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, Nov 11 2012 Notes: doi: 10.1038/nm.2984.
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.
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.
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.
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, Aug 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, Oct 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, Dec 2009.
Yin, L, Wang, J, Klein, PS, and Lazar, MA. : Nuclear receptor Rev-erbα is a Critical Lithium-Sensitive Component of the Circadian Clock. Science 311(5763): 1002-5. Feb 2006.
Wu J, O'Donnell M, Gitler AD, and PS Klein: Kermit-2/XGIPC, an IGF1R interacting protein, is required for IGF signaling in Xenopus eye development. Development 133: 3651-3660, 2006.
O'Brien, W.T., Harper,A.D., Jove, F., Woodgett, J.R., Maretto, S., Piccolo, S., and P.S. Klein: Glycogen synthase kinase-3ß haploinsufficiency mimics the behavioral and molecular effects of lithium. Journal of Neuroscience 24: 6791– 6798, 2004.
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Last updated: 10/03/2014
The Trustees of the University of Pennsylvania
Last updated: 10/03/2014
The Trustees of the University of Pennsylvania


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In the first week of the Supreme Court's 2014-2015 term lurks an easy-to-miss case. Integrity Staffing Solutions, Inc. v. Busk reveals the ugly side of business today.
The last time the group of missing students were seen was in the custody of Mexican municipal police forces, who detained them after opening fire on their caravan.
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House, White House aim for $32-$35 billion in farm bill cuts
As time runs out to pass a new U.S. Farm Bill in 2012, the White House and Republicans in the House of Representatives hold surprisingly similar goals about how much to cut spending - roughly from $32 billion to $35 billion.
But getting to a final agreement is proving difficult. Each side agrees to significant cuts to farm subsidies and soil conservation, but they have diametrically different views on food stamps, which the White House refuses to cut.
A final figure for cuts may emerge as part of an agreement on government-wide retrenchment to rein in the federal deficit.
House Republican leaders and the White House continued to squabble on Monday over elements for a broad deficit reduction package.
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Both sides would eliminate the $5 billion-a-year direct-payment subsidy, also a top target of reformers. And they would reduce funds for conservation.
The near-agreement on the size of cuts is obscured by infighting over funding for food stamps and how broadly to rewrite the farm program, a small-farm activist said on Monday.
"There is some coincidence" in the goal, said Dale Moore of the 6-million-member American Farm Bureau Federation, arising from similar views about agriculture's potential share of cut-backs. But there is sharp disagreement over which programs to cut.
The White House would cut crop subsidies, crop insurance and conservation but not food stamps for the poor. The farm bill approved by the House Agriculture Committee would get half of its $35 billion in savings from food stamps and the rest from crop subsidies and conservation. Some Republicans would cut deeper still into food stamps.
In its proposal, the White House said it would save $7.5 billion on crop insurance over 10 years, $30 billion by ending the direct payment and $2 billion on conservation. It would use some of the savings to pay for disaster-relief programs.
On Monday, House Republican leaders suggested budget cuts patterned on an unsuccessful 2011 budget reform commission on top of automatic spending cuts scheduled to take effect in January. The automatic cuts would trim farm programs by as much as $10 billion. The commission's plan suggested $10 billion in cuts and cited farm subsidy, conservation and export promotion programs as potential targets.
House action on the farm bill stalled during the summer. The Senate passed its bill in mid-June with a lower overall spending cut of $23 billion. It would cut crop subsidy spending by $13 billion over 10 years and reduce the premium subsidy for crop insurance policies purchased by big operators, while paring the food stamp budget by $4 billion.
(Reporting By Charles Abbott; Editing by Eric Walsh)
Buyers Guide
Comments (11) Leave a comment
If only we farmers would realize this is a welfare bill and not a farm bill, we may come to our senses and stop pushing congress to pass this. Since there is very little to do with agriculture in this bill, perhaps they should appropriately name it the Obama Welfare-Care Bill.
totally agree....food stamps should be pert of health & human services
Let's operate like other small bussiness america. We shouldn't have to have the american tax payers pay our crop insurance or pay anything other than a consevation program when you have record commidoty prices and all of this is leading to commodity prices to bust! when you look at the pasture land and crp that is being broken up just because of all the handouts to the American farmer. Let's ask for the help when we nead it. Lets adjust the food stamp program and help those that are trying to help themselves.
Sounds like they want to bite the hand that feeds them!! Farmers will always provide for their families and friends, food stamp folks will have to hungry!!
TDI, Obama did not start the Food stamp program. It was started 80 years ago and really came to life 40 years under the direction of Bob Dole, a Republican. check out this Youtube http://www.youtube.com/watch?v=-0_OWueb_8Y Yes, there are those who abuse it, but the waste here is nothing compared to farm subsidies. Anytime you hang money on a tree, everyone, including the rich, try to pick it. Most of us who farm agree that the Food stamp program needs to be moved to the health and human services....good luck getting that done
do u now what cost a farmer? seed fertilizer machinery chemicals etc. thia stuff all has to be paid for plus their living. they feed the WORLD plus u.
It's hard to find any well used equipment in a farmers yard. When i started farming it was all used. I think there is plenty of money to live off of. Let's be honest and do our share not going over the cliff.
Guess you are in the wrong neighborhood....all of our equipment is pretty well run out and run down and any major breakdown will create a financial crisis....this is pretty typical of our country's small dairies, where it is hard to remember a good year....
Makes no difference where they fund food stamps....it's all federal budget...it's just that the public should know that the farm bill is not all for farm subsidies....wonder how many dairy farmers are eligible for food stamps...nobody in this country or otherwise should be hungry!!
You might be surprised at how many dairy families qualify for food stamps (but don't use them) ... the numbers are staggering on what dairy farm families live on compared to the rest of society. Most people think of farmers as "big" crop farmers. That drives farm programs as well as public sentiment. I am so tired of seeing WIC / food stamp abuse. Obese people use their food stamps in convenience stores to buy subs, chips and hi sugar drinks. Then whip out cash to pay for cigarettes and beer. Food and Nutrition programs need to be moved out of Farm Bill and need to be restructured to be a voucher program for staples - bread, milk, eggs, fresh produce, potatoes, flour, cereal, and some dried goods (beans, rice, etc.). Why should people be using food assistance for expensive (often unhealthy) food choices that are convenient, prepackaged, boxed or fozen meals, etc. On the farm side, farmers don't need to be paid subsidies in years with high net farm income for their enterprise. Some conservation dollars are wasteful - why are we paying for set aside land in areas that are not environmentally sensitive? Conservation funding is important but needs to be prioritized better. Crop insurance benefits the insurance industry most - who lobbied strongest for that - farmers or insurance reps and lawyers? The most important thing in the farm bill is the disaster program. When a disaster (natural or man-made) hits - farmers need assistance to get back on their feet and back to production. Everything in the federal budget (including salaries of feds) should be on the chopping block - but lets be smart and fair about it-cut the waste and abuse. The best cuts would be to decrease the size and operation cost of the fed govt.
Does the field of efficiency expert still exist? Maybe we need quite desperately to use some of them to streamline government agencies. Then get fraud experts to find the fraud, waste, and manipulation of ALL 'help' programs from WIC right on through crop subsidies, to government employees, even our elected officials, to assure OUR money is going where truly needed. IMO, many farm programs will still exist.......since Ag producers typically make 1.5 to 3.0% on their personal investment, at best. Are there any other small business, besides agriculture, that DO NOT get any government subsidies????
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The Lake District - Keswick
- The official visitor site for Keswick.
- Watch our new video and be tempted to book that break
- Book direct with any Keswick the Lake District Hotel, B&B or self catering cottage displaying the Fair Booking Keswick Logo for the best accommodation deal for customers and a better deal for the local tourism economy.
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