Rheumatology, Immunology and Allergy
- A.B., Washington University, St. Louis, 1979
- Ph.D., University of Alabama at Birmingham, 1985
- Publications Committee, American Association of Immunologists, Section Editor, Journal of Immunology; Ad hoc Reviews: NIAID, NSF, Special Emphasis Panel (NIH), Gene, International Immunology, Molecular Immunology, Nucleic Acids Research, Journal of Biological Chemistry
- American Association of Immunologists (AAI)
- American Society for Microbiology (ASM)
- American Association for the Advancement of Science (AAAS)
- American College of Rheumatology (ACR)
- Federation of Clinical Immunology
- International Society for Stem Cell Research
My laboratory currently has several areas of focus. Before I moved to OMRF, I discovered a protein called ARID3a, or Bright, in the white blood cells called B lymphocytes. B lymphocytes are the cells that make antibodies. Antibodies are the protective proteins that are made when individuals are immunized. ARID3a was first discovered as a protein that helps regulate antibody production. However, we now know that it plays important roles in many other types of cells than B lymphocytes. Each of our projects is focused on understanding what ARID3a does in different kinds of cells.
- Michelle Ratliff, PhD - Postdoctoral Fellow
- Josh Garton - Graduate Student
- M. David Barron - Graduate Student
- Malini Shankar, MS - Laboratory Manager
- Brittany Chapman, MS - Laboratory Technician
ARID3a in Lupus:
One of our projects involves studying how ARID3a contributes to autoimmune disease. Lupus is an autoimmune disease that results in abnormal antibody production. We now know that many patients with lupus have increased amounts of ARID3a in their B lymphocytes. Preliminary data also indicates ARID3a expression is increased in granulocytes, specifically plasmacytoid dendritic cells and low density neutrophils. A major goal of my lab is to learn why ARID3a is over-expressed in blood cells from lupus patients. We hope that these results eventually will lead to better treatments for people with lupus.
Induced Pluripotent Stem Cells:
The second major project in my lab involves adult stem cells. To our surprise, we discovered a number of years ago, that mice lacking ARID3a have adult tissues that can be induced to develop into other cell types. For example, skin cells could be induced to become cells that look more like nerve cells. This process is called reprogramming and is the basis for exciting new research in regenerative medicine. We do not understand how ARID3a levels cause changes in cells that allow them to be manipulated to make other cell types. Our current research focuses on learning how ARID3a can be used in regenerative medicine studies. This exciting area of research may eventually lead to new therapies for people with damaged tissues.
ARID3a in Kidney Regeneration:
Our lab is also working with collaborators to understand how kidney development occurs. Using a special mouse cell line that doesn’t express ARID3a produced in my lab, we are learning what is necessary to form different parts of the kidney. We have recently moved into studies using human kidney tissues. Many diseases, including lupus and diabetes, eventually result in damage that affects kidney function. We expect the information we learn will be useful for understanding how to repair damaged kidneys.
Determination of ARID3a Interacting Proteins:
Our data showed that ARID3a was required for normal blood cell development, as well as the normal development of other white blood cells, in both mice and human cells. Although most proteins related to ARID3a function in association with large protein complexes that alter gene expression by changing chromatin structures, nothing is known about the protein complexes associated with ARID3a in hematopoietic stem cells. These studies will identify ARID3a-associated proteins and provide important insights into how ARID3a may regulate hematopoiesis in human cells.
- Ward, J.M., Ratliff, M.L., Dozmorov, M.G., Wiley, G., Guthridge, J.M., Gaffney, P.M., James, J.A., and Webb, C.F. Human effector B lymphocytes express ARID3a and secrete interferon alpha. Journal of Autoimmunity. 2016 Aug 10.
- Ward, J.M., Ratliff, M.L., Dozmorov, M.G., Wiley, G., Guthridge, J.M., Gaffney, P.M., James, J.A., and Webb, C.F. Expression and methylation data from SLE patient and healthy control blood samples subdivided with respect to ARID3a levels. Data in Brief. 2016 Aug 31;9:213-9.
- Ratliff, M.L., Mishra, M., Frank, M.B., Guthridge, J.M., and Webb, C.F. The Transcription Factor ARID3a is Important for In Vitro Differentiation of Human Hematopoietic Progenitors. J immunol 2016 Jan 15; 196(2):614-23.
- *Webb CF, Ratliff ML, Powell R, Wirsig-Wiechmann CR, Lakiza O, Obara T. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures. Biochem Biophys Res Commun. 2015 Aug 7;463(4):1334-40. [Abstract]
- * Ratliff, M. L., J. M. Ward, J. T. Merrill, J. A. James, and C. F. Webb. 2015. Differential Expression of the Transcription Factor ARID3a in Lupus Patient Hematopoietic Progenitor Cells. J Immunol 194: 940-949. [Abstract]
- * Ward JM, Rose K, Montgomery C, Adrianto I, James JA, Merrill JT, Webb CF. Disease activity in lupus correlates with expression of the transcription factor AT-Rich-Interactive Domain 3a. Arthritis Rheumatol 66:3404-3412, 2014. [Abstract] EPub [Supplementary Data]
- Ratliff ML, Templeton TD, Ward JM, Webb CF. The Bright side of hematopoiesis: regulatory roles of ARID3a/Bright in human and mouse hematopoiesis. Front Immunol 5:113, 2014. [Abstract]
- Popowski M, Templeton TD, Lee BK, Rhee C, Li H, Miner C, Dekker JD, Orlanski S, Bergman Y, Iyer VR, Webb CF, Tucker H. Bright/Arid3A acts as a barrier to somatic cell reprogramming through direct regulation of Oct4, Sox2, and Nanog. Stem Cell Reports 2:26-35, 2014. [Article]
- * Guthridge JM, Lu R, Sun H, Sun C, Wiley GB, Dominguez N, Macwana SR, Lessard CJ, Kim-Howard X, Cobb BL, Kaufman KM, Kelly JA, Langefeld CD, Adler AJ, Harley IT, Merrill JT, Gilkeson GS, Kamen DL, Niewold TB, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vila LM, Kimberly RP, Freedman BI, Stevens AM, Boackle SA, Criswell LA, Vyse TJ, Behrens TW, Jacob CO, Alarcon-Riquelme ME, Sivils KL, Choi J, Joo YB, Bang SY, Lee HS, Bae SC, Shen N, Qian X, Tsao BP, Scofield RH, Harley JB, Webb CF, Wakeland EK, James JA, Nath SK, Graham RR, Gaffney PM. Two Functional Lupus-Associated BLK Promoter Variants Control Cell-Type- and Developmental-Stage-Specific Transcription. Am J Hum Genet 94:586-598, 2014. [Abstract]
- Oldham AL, Miner CA, Wang HC, Webb CF. The transcription factor Bright plays a role in marginal zone B lymphocyte development and autoantibody production. Mol Immunol 49:367-379, 2011. [Abstract]
- Webb CF, Bryant J, Popowski M, Allred L, Kim D, Harriss J, Schmidt C, Miner CA, Rose K, Cheng HL, Griffin C, Tucker PW. The ARID family transcription factor Bright is required for both hematopoietic stem cell and B lineage development. Mol Cell Biol 31:1041-1053, 2011. [Abstract]
- An G, Miner CA, Nixon JC, Kincade PW, Bryant J, Tucker PW, Webb CF. Loss of Bright/ARID3a function promotes developmental plasticity. Stem Cells 28:1560-1567, 2010. [Abstract]
- Schmidt C, Kim D, Ippolito GC, Naqvi HR, Probst L, Mathur S, Rosas-Acosta G, Wilson VG, Oldham AL, Poenie M, Webb CF, Tucker PW. Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright. EMBO J 28:711-724, 2009. [Abstract]
View all publications in PubMed