Robert F. Paulson

About Me

I have a BA in Biochemistry, Molecular and Cell Biology from Northwestern University. After graduation I went in to do a PhD in Biochemistry at the University of California-San Francisco. I did my thesis on the role tyrosine kinase signaling in Drosophila Development in the laboratory of Michael Bishop. I was a postdoctoral fellow at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto Canada, where I studied hematopoiesis in the lab of Alan Bernstein. Much of my postdoctoral work focused on cell signaling during mast cell development with side projects on the genetics of leukemia progression and mechanisms that regulate erythropoiesis. Since establishing my own lab at Penn State in 1998, my lab has focused on erythropoiesis. In particular, we study the response to anemia, which is called stress erythropoiesis. We also have collaborative projects to investigate new anti-leukemic drugs. I have progressed up the academic ranks and am a full Professor in the Department of Veterinary and Biomedical Sciences. I am a member of the BMMB graduate program, the MCIBS and the Molecular physiology graduate programs.   

Department or University Committees

• University Isotope Committee
   
• Chair MCIBS steering committee
   
• Transgenic mouse facility steering committee
   
• VBSC Departmental Promotion and Tenure Committee

Program or Departmental Affiliations

Editorial Boards and Professional Organizations

Centers

Research Summary

Work in the Paulson lab focuses on the mechanisms that regulate tissue regeneration. Throughout adult life, tissues become damaged and must be repaired or regenerated to maintain homeostasis. We focus on the maintenance of erythrocytes or red blood cells. Steady state erythropoiesis generates new erythrocytes at a constant rate, more than 10⁶/second. Despite this enormous capacity, there are times when this process cannot produce enough erythrocytes. For example, infection inhibits this process and in response to anemia the bone marrow production of erythrocytes is not sufficient to maintain normal blood levels. At these times stress erythropoiesis rapidly produces large numbers of erythrocytes to maintain homeostasis until the bone marrow can resume production. This process is a stem cell mediated process as hematopoietic stem cells directly generate stress erythroid progenitors. Furthermore, the signals that regulate this process are distinct from steady state erythropoiesis and are more associated with embryonic development than hematopoiesis suggesting that stress erythropoiesis is similar to other tissue regeneration processes.

Research in the Paulson lab focusses on two aspects of stress erythropoiesis. The first set of projects deal with how signals from the microenvironment regulate the commitment of stem cells to the stress erythroid lineage, promote the proliferation of a transient amplifying population of immature progenitors while at the same time inhibiting their differentiation and regulate the transition proliferating progenitors to differentiating progenitors, which terminally differentiation (See Image 1). We have identified key signals at each stage of this process and have developed in vitro and in vivo models to study stress erythropoiesis. In addition, we have demonstrated that stress erythroid progenitors develop in a specialized niche in the spleen and have characterized several key signals that regulate the development of this niche. Our future work will examine how the development of the niche is coordinated with the development of the progenitor cells. The second set of projects deal with the role of stress erythropoiesis in disease. We are focusing on the role of stress erythropoiesis in chronic anemia caused by inflammation and infection, which is a major cause of anemia worldwide. We are using in vivo models of inflammatory anemia to understand how stress erythropoiesis is regulated in these disease conditions and how manipulation of this pathway could be used to treat the anemia.  

Honors and Awards

• Phi Beta Kappa
   
• David C. Rae Memorial Fellow of the Leukemia Research Fund of Canada

Selected Publications

• BMP4 and Madh5 regulate the erythroid response to acute anemia. L Lenox, J Perry and RF Paulson. (2005) Blood 105: 2741-2748.
   
• Murine erythroid short term radioprotection requires a BMP4 dependent, self-renewing population of stress erythroid progenitors. O. Harandi, S. Hegde, D. Wu, D. Mckeone and RF Paulson. Journal of Clinical Investigation(2010) 120:4507–4519.
   
• In vitro expansion of stress erythroid progenitors identifies distinct progenitor populations and analogous human stress erythroid progenitors. J Xiang, DC Wu, Y. Chen and RF Paulson. (2015) Blood 125:1803-1812.
   
• Monocyte derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia. Liao, C, Prabhu, KS and Paulson, RF. Blood 2018 132:2580-2593.
   
• Inflammation induces stress erythropoiesis through heme dependent activation of Spi-C. Bennett LF, Liao C, Quickel MD, Yeoh BS, Vijay-Kumar M, Hankey-Giblin P, Prabhu KS, and Paulson RF. Science Signaling 2019 12(598). pii: eaap7336. doi: 10.1126/scisignal.aap7336.
   
• Δ¹²-prostaglandin J₃, an omega-3 fatty acid-derived endogenous metabolite, selectively ablates leukemia stem cells in mice. SN Hegde, N Kaushal, RC Kodihalli, C Chiaro, KT Hafer, UH Gandhi, JT Thompson, JP Vanden Heuval, MJ Kennett, P Hankey, RF Paulson, and KS Prabhu. Blood (2011) 118:6909-6919.
   
• Activation of PPARγ by endogenous prostaglandin J2 mediates the antileukemic effect of selenium in murine leukemia. Finch ER, Tukaramrao DB, Goodfield LL, Quickel MD, Paulson RF, Prabhu KS. Blood. (2017) 129: 1802-1810.