Joined the Department in 2010
- B.A., 1977, Pomona College, Physics.
- Ph.D., 1983, Caltech, Biology.
- Postdoctoral research, University of California, San Diego.
- Previous faculty appointments: Rice University, Baylor College of Medicine, Howard Hughes Medical Institute.
Tissue size regulation, tissue cell composition, and fibrosing diseases
Our laboratory is working on three areas of biomedicine, trying to move observations from basic research into the clinic. First, we are studying how the sizes of tissues and tumors are regulated, and how this can be manipulated for therapeutic purposes. As a model system, we are using the simple eukaryote Dictyostelium discoideum, which allows us to combine techniques such as biochemistry, genetics, computer modeling, and cell biology to study tissue size regulation. We have found that a secreted protein as well as the unusual molecule polyphosphate are signals in negative feedback loops that inhibit Dictyostelium cell proliferation, and we are studying the signal transduction pathway to understand similar mechanisms in humans.
Second, we are studying how some secreted proteins can make cells move away from the source of the signal. We found such a signal (called a chemorepellent) in Dictyostelium, and then found a similar signal in humans. We are working to understand the signal transduction pathway for both. The human signal repels neutrophils, and we found that this can be used therapeutically in mouse models of neutrophil-driven diseases such as rheumatoid arthritis and acute respiratory distress syndrome.
Third, we have found that a human blood protein called Serum Amyloid P (SAP) regulates a key step in the formation of scar tissue as well as the formation of the scar-like lesions in fibrosing diseases such as congestive heart failure and pulmonary fibrosis. We are studying this mechanism, and a biotech company (Promedior) we co-founded is testing SAP as a therapy for fibrosis in patients in two Phase 2 trials.
- Kirolos, SA, Rijal, R, Consalvo, KM, Gomer, RH. Using Dictyostelium to Develop Therapeutics for Acute Respiratory Distress Syndrome. Front Cell Dev Biol. 2021;9 :710005. doi: 10.3389/fcell.2021.710005. PubMed PMID:34350188 PubMed Central PMC8326840.
- McCullough, J, Fey, P, Rahman, RJ, Wallace, M, Morey, S, Sahlberg, K et al.. Annotating Putative D. discoideum Proteins Using I-TASSER. MicroPubl Biol. 2021;2021 :. doi: 10.17912/micropub.biology.000420. PubMed PMID:34278246 PubMed Central PMC8280847.
- Tang, Y, Rijal, R, Zimmerhanzel, DE, McCullough, JR, Cadena, LA, Gomer, RH et al.. An Autocrine Negative Feedback Loop Inhibits Dictyostelium discoideum Proliferation through Pathways Including IP3/Ca2. mBio. 2021;12 (3):e0134721. doi: 10.1128/mBio.01347-21. PubMed PMID:34154396 PubMed Central PMC8262924.
- Karmakar, R, Tyree, T, Gomer, RH, Rappel, WJ. Cell dispersal by localized degradation of a chemoattractant. Proc Natl Acad Sci U S A. 2021;118 (6):. doi: 10.1073/pnas.2008126118. PubMed PMID:33526658 PubMed Central PMC8017704.
- Karhadkar, TR, Pilling, D, Gomer, RH. Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice. PLoS One. 2021;16 (1):e0245924. doi: 10.1371/journal.pone.0245924. PubMed PMID:33481950 PubMed Central PMC7822324.
- Pilling, D, Karhadkar, TR, Gomer, RH. A CD209 ligand and a sialidase inhibitor differentially modulate adipose tissue and liver macrophage populations and steatosis in mice on the Methionine and Choline-Deficient (MCD) diet. PLoS One. 2020;15 (12):e0244762. doi: 10.1371/journal.pone.0244762. PubMed PMID:33378413 PubMed Central PMC7773271.
- Rijal, R, Cadena, LA, Smith, MR, Carr, JF, Gomer, RH. Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells. Proc Natl Acad Sci U S A. 2020;117 (50):31923-31934. doi: 10.1073/pnas.2012009117. PubMed PMID:33268492 PubMed Central PMC7749317.
- Karhadkar, TR, Meek, TD, Gomer, RH. Inhibiting Sialidase-Induced TGF-β1 Activation Attenuates Pulmonary Fibrosis in Mice. J Pharmacol Exp Ther. 2021;376 (1):106-117. doi: 10.1124/jpet.120.000258. PubMed PMID:33144389 PubMed Central PMC7788355.
- Pilling, D, Karhadkar, TR, Gomer, RH. High-Fat Diet-Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice Are Reduced by Inhibiting Sialidases. Am J Pathol. 2021;191 (1):131-143. doi: 10.1016/j.ajpath.2020.09.011. PubMed PMID:33039353 PubMed Central PMC7786079.
- Karhadkar, TR, Pilling, D, Gomer, RH. Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice. bioRxiv. 2020; :. doi: 10.1101/2020.08.26.269183. PubMed PMID:32869032 PubMed Central PMC7457621.