Katherine Swenson-Fields, Ph.D.

Professional Background

Dr. Katherine Swenson-Fields received her BS and Ph.D. in Microbiology at the University of Washington before pursuing postdoctoral training in the Department of Anatomy and Cell Biology at Harvard Medical School. She subsequently joined the faculty at Duke University Medical Center as an Assistant Professor prior to moving to the University of Kansas Medical Center in 2008 when she joined the Department of Anatomy and Cell as an Associate Research Professor.

• BS, Microbiology, University of Washington, Seattle, WA
• Ph.D., Microbiology, University of Washington, Seattle, WA
• Post Doctoral Fellowship, Anatomy and Cell Biology, Harvard Medical School, Boston, MA

Research

Overview

Our studies, which are carried out in collaboration with Dr. Timothy Fields, M.D., Ph.D., are focused on the role of the innate immune environment in polycystic kidney disease (PKD) with the broad goal of identifying new pathways that promote disease progression and validating therapeutic agents that target these pathways in preclinical studies. Much of our work is concerned with macrophages, which are innate immune cells present in all tissues where they have critical roles in surveillance and in producing rapid immune responses following infection or injury. At later times following these insults, these cells also begin to produce factors that promote repair, cell proliferation and regeneration of damaged tissues. In PKD our studies have shown that macrophages, in carrying out regenerative functions within these diseased kidneys, actually are maladaptive, acting to promote cyst cell proliferation, cyst expansion and functional renal decline. We think that the mechanisms by which macrophages become regenerative and the specific factors produced by these cells are likely to be useful novel targets for the development of therapeutic agents designed to slow cystic disease progression.

In other studies of the innate immune response in PKD, we have found that inflammasomes, which are key initiators of inflammation that are found primarily within immune cells, are activated at early stages of PKD. Using a human-orthologous mouse model of PKD we have knocked-out the Caspase1 gene, which encodes the essential enzyme required for inflammasome activation, and have found that cyst formation and disease progression are dramatically restrained specifically in female mice. Early results from ongoing pre-clinical studies using an inflammasome inhibitor to treat cystic disease in mice suggest that this innate immune pathway may be a relevant target for therapy in PKD.

Recent Publications

• Swenson-Fields KI, Vivian CJ , Salah SM, Peda JD, Davis BM, van Rooijen N, Wallace DP, and Fields TA. (2013) Macrophages Promote Polycystic Kidney Disease Progression. Kidney International 83, 855-864; PMID: 23423256.
• Chen L, Zhou X, Fan LX, Yao Y, Swenson-Fields KI, Gadjeva M, Wallace DP, Peters DJM, Yu A, Grantham JJ and Li X (2015) Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease. (2015) Journal of Clinical Investigation 125, 2399-2412.
• Peda JD, Salah SM, Wallace DP, Fields PE, Grantham CJ, Fields TA and Swenson-Fields KI. (2016) Autocrine IL-10 activation of the STAT3 pathway is required for pathological macrophage differentiation in polycystic kidney disease. Dis Model Mech 9:1051-1061.
• Salah SM, Meisenheimer JD, Rao R, Peda JD, Wallace DP, Foster D, Li X, Li X, Zhou X, Fields TA and Swenson-Fields KI. (2019) MCP-1 Promotes Detrimental Cardiac Physiology, Pulmonary Edema and Death in the cpk model of Polycystic Kidney Disease. American Journal of Physiology-Renal Physiology. 317:F343-F360. PMCID: PMC6732452
• Swenson-Fields KI, Ward CJ, Lopez ME, Fross S, Dillon AL, Meisenheimer JD, Rabbani AJ, Wedlock E, Basu MK, Jansson KP, Rowe PS, Stubbs JR, Wallace DP, Vitek VP and Fields TA (2022) Caspase-1 and the inflammasome promote polycystic kidney disease progression. Frontiers in Molecular Biosciences 9:971219. doi: 10.3389/fmolb.2022.971219

Contributions to Science

1. The early research of Dr. Katherine Swenson-Fields, both as a postdoctoral fellow and instructor at Harvard Medical School was focused on the cyclins and regulation of meiosis and early embryonic divisions. Her four publications in this area listed below, collectively have over 1,000 citations. In 1986, her paper showed the first cyclin sequence (Cyclin A) and demonstrated the ability of its encoded protein to drive cells into M phase of the cell cycle. This paper has been cited nearly 500 times, and the work was cited by a panel of scientists as part of one of the 23 seminal discoveries in the past 100 years in the field of cell division (http://www.nature.com/celldivision/milestones/index.html).
   1. Swenson KI, Farrell KM, and Ruderman JV. 1986. The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. Cell 47:861-870.
   2. Westendorf JM, Swenson KI and Ruderman JV. 1989. The role of cyclin B in meiosis I. J Cell Biol 108:1431-1444.
   3. Parker LL, Atherton-Fessler S, Lee MS, Ogg S, Falk JL, Swenson KI and Piwnica-Worms H. 1991. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner. EMBO J 10:1255-1263.
   4. Roy LM, Swenson KI, Walker DH, Gabrielli BG, Li RS, Piwnica-Worms H and Maller JL. 1991. Activation of p34cdc2 kinase by cyclin A. J. Cell Biol 113:507-514.
2. Dr. Swenson-Fields has also made significant contributions to the understanding of gap junctions. She and her co-workers were among the first groups to clone the genes for gap junction proteins and to study the formation and regulation of gap junction channels following expression of these genes in paired Xenopus oocytes. The four publications listed below collectively have more than 1,000 citations.
   1. Swenson KI, Jordan FR, Beyer EC and Paul DL. 1989. Formation of gap junctions by expression of connexins in Xenopus oocyte pairs. Cell 57:145-155.
   2. Ebihara L, Beyer EC, Swenson KI, Paul DL and Goodenough DA. 1989. Cloning and expression of a Xenopus embryonic gap junction protein. Science 243:1194-1195.
   3. Swenson KI, Piwnica-Worms H, McNamee H, and Paul DL. 1990. Tyrosine phosphorylation of the gap junction protein connexin43 is required for the pp60v-src-induced inhibition of communication. Cell Regul 1(13):989-1002.
   4. Paul DL, Ebihara L, Takemoto LJ, Swenson KI and Goodenough DA. 1991. Connexin 46, a novel lens gap junction protein, induces voltage-gated currents in non-junctional plasma membrane of Xenopus oocytes. J Cell Biol 115: 1077-1089.
3. As a faculty member at Duke, Dr. Swenson-Fields made other contributions to understanding cell division. She helped define the function of an important prolyl isomerase in mitosis regulation. She also uncovered a new function for a previously known MAPK family member in cell-cycle regulated cytoskeletal organization.
   1. Winkler KE, Swenson KI, Kornbluth S and Means, AR. 2000. Requirement of the prolyl isomerase Pin1 for the replication checkpoint. Science 287: 1644-1647.
   2. Swenson KI, Winkler KE and Means AR. 2003 A new identity for MLK3 as an NIMA-related, Cell cycle-regulated kinase that is localized near centrosomes and influences microtubule organization. Mol Biol Cell 14: 156-172.
4. Dr. Swenson-Fields has also made contributions that have advanced the area of cellular signaling impacting cytoskeletal organization and contractile forces. She defined a kinase-independent role for a MAPK in controlling Gq activation by GPCRs to influence cytoskeletal organization and cell migration. This publication (Mol Cell 32:23) was selected as an “Editor’s choice” by Science Signaling (http://stke.sciencemag.org/content/1/42/ec362). In another highly cited study, she helped define the differential regulatory pathways and functions of the two primary isoforms of non-muscle myosin II in cell rounding and migration.
   1. Swenson-Fields KI, Sandquist JC, Rossol-Allison J, Blat IC, Wennerberg K, Burridge K and Means AR. MLK3 limits activated Gaq signaling to Rho by binding to p63RhoGEF. Mol Cell 32(1):43-56, 2008. PMCID: PMC2603627
   2. Sandquist JC, Swenson KI, Demali KA, Burridge K and Means AR. 2006. Rho kinase differentially regulates phosphorylation of nonmuscle myosin II isoforms A and B during cell rounding and migration. J Biol Chem 281: 35873-35883.
5. Since coming to the University of Kansas Medical Center, Dr. Swenson-Field's research has focused on understanding the pathologic processes, which promote proliferation in polycystic kidney disease, especially the contribution of inflammation to these processes. She has shown that renal macrophages promote cyst cell proliferation, cyst expansion, and renal functional decline in PKD. She was a pioneer in the development of this concept which is recognized in the most current models of disease pathogenesis (PMC3871779), and the publication was selected by Faculty of 1000 as having special significance in the field (http://f1000.com/prime/717980903?bd=1&ui=27410). Most recently Dr. Swenson-Fields has identified the inflammasome pathway and Caspase 1, the enzyme which mediates inflammasome activity, to be important contributors to disease progression in PKD.
   1. Grantham JJ, Mulamalla S and Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nature Reviews Nephrology doi: 7(10):556-56, 2011.  PMCID: PMC3386669
   2. Swenson-Fields KI, Vivian CJ , Salah SM, Peda JD, Davis BM, van Rooijen N, Wallace DP, and Fields TA. (2013) Macrophages promote polycystic kidney disease progression. Kidney Int 83:855-864. PMCID: PMC4028685
   3. Peda JD, Salah SM, Wallace DP, Fields PE, Grantham CJ, Fields TA and Swenson-Fields KI. (2016) Autocrine IL-10 activation of the STAT3 pathway is required for pathological macrophage differentiation in polycystic kidney disease. Dis Model Mech 9:1051-1061. PMCID: PMC5047688
   4. Salah SM, Meisenheimer JD, Rao R, Peda JD, Wallace DP, Foster D, Li X, Li X, Zhou X, Fields TA and Swenson-Fields KI. (2019) MCP-1 Promotes Detrimental Cardiac Physiology, Pulmonary Edema and Death in the cpk model of Polycystic Kidney Disease. American Journal of Physiology-Renal Physiology. 317:F343-F360. PMCID: PMC6732452
   5. Swenson-Fields KI, Ward CJ, Lopez ME, Fross S, Dillon AL, Meisenheimer JD, Rabbani AJ, Wedlock E, Basu MK, Jansson KP, Rowe PS, Stubbs JR, Wallace DP, Vitek VP and Fields TA (2022) Caspase-1 and the inflammasome promote polycystic kidney disease progression. Frontiers in Molecular Biosciences 9:971219. doi: 10.3389/fmolb.2022.971219