Academic Section(s):
Rheumatology, Immunology and Allergy
Education:
- A.B., Washington University, St. Louis, 1979
- Ph.D., University of Alabama at Birmingham, 1985
Other Activities
- 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
Memberships
- 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
Clinical/Research Interests:
Research Summary:
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.
Current and Former Lab Members:
- James Hocker, MS
- Jared Ruth
- Michelle Ratliff, PhD
- Josh Garton
- M. David Barron
- Malini Shankar, MS
- Brittany Chapman, MS
- Julie Ward, PhD
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.
Select Publications:
Recent Publications
- Garton J, Shankar M, Chapman B, Rose K, Gaffney PM, Webb CF. Deficiencies in the DNA Binding Protein ARID3a Alter Chromatin Structures Important for Early Human Erythropoiesis. Immunohorizons. 2021 Oct 18;5(10):802-817. doi:10.4049/immunohorizons.2100083. PMID: 34663594; PMCID: PMC8900713.
- Ratliff ML, Shankar M, Guthridge JM, James JA, Webb CF. TLR engagement induces ARID3a in human blood hematopoietic progenitors and modulates IFNα production. Cell Immunol. 2020 Nov;357:104201. doi:10.1016/j.cellimm.2020.104201. Epub 2020 Sep 9. PMID: 32979763; PMCID: PMC7737244.
- Ratliff ML, Garton J, James JA, Webb CF. ARID3a expression in human hematopoietic stem cells is associated with distinct gene patterns in aged individuals. Immun Ageing. 2020 Sep 3;17:24. doi: 10.1186/s12979-020-00198-6. PMID: 32905435; PMCID: PMC7469297.
- Garton J, Barron MD, Ratliff ML, Webb CF. New Frontiers: ARID3a in SLE. Cells. 2019 Sep 24;8(10):1136. doi: 10.3390/cells8101136. PMID: 31554207; PMCID: PMC6830313.
- Molineros JE, Singh B, Terao C, Okada Y, Kaplan J, McDaniel B, Akizuki S, Sun C, Webb CF, Looger LL, Nath SK. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility. Front Immunol. 2019 May 20;10:1066. doi:10.3389/fimmu.2019.01066. PMID: 31164884; PMCID: PMC6536009.
- Julio E. Molineros, Bhupinder Singh, Chikashi Terao, Yukinori Okada, Jakub Kaplan, Barbara McDaniel, Shuji Akizuki, Celi Sun, Carol Webb, Loren L. Looger, Swapan K. Nath Mechanistic characterization of RASGRP1 variants identifies an hnRNP K-regulated transcriptional enhancer contributing to SLE susceptibility Now published in Frontiers in Immunology doi: 10.3389/fimmu.2019.01066 doi: https://doi.org/10.1101/568790
- Shah HB, Smith K, Wren JD, Webb CF, Ballard JD, Bourn RL, James JA, Lang ML. Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires. Front Immunol. 2019 Jan 15;9:3064. doi: 10.3389/fimmu.2018.03064. PMID: 30697210; PMCID: PMC6340933.
- Ratliff ML, Garton J, Garman L, Barron MD, Georgescu C, White KA, Chakravarty E, Wren JD, Montgomery CG, James JA, Webb CF. ARID3a gene profiles are strongly associated with human interferon alpha production. J Autoimmun. 2019 Jan;96:158-167. doi: 10.1016/j.jaut.2018.09.013. Epub 2018 Oct 5. PMID: 30297159; PMCID: PMC6497177.
Selected Publications
- 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.
- 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.
- 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]
- 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]
- 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]