Alfred H.J. Kim, M.D., Ph.D.

Assistant Professor
Internal Medicine
Pathology and Immunology

Immunology Program

Research Abstract:

The Kim laboratory research program is primarily interested in identifying the role of cytokines in glomerular injury. Our work has recently shown that cytokines play a critical role in the initiation of glomerular injury in steroid-sensitive nephrotic syndromes such as minimal change disease, and identified novel targets for therapeutic intervention. These data have wide-reaching impact on all glomerular diseases, including glomerulonephritis.

In addition, we have projects utilizing state-of-the-art imaging approaches to investigate immunologic processes in the kidney:
--One arm is utilizing tissue clearing approaches to render kidneys completely transparent. When coupled with multiphoton microscopy, the entire kidney can be imaged yielding important information about immune cell architecture.
--Another arm is imaging renal macrophage activation non-invasively within mice utilizing near-infrared optical imaging (in collaboration with Walter Akers, Mallinckrodt Institute of Radiology, WashU). Inflammatory renal diseases such as glomerulonephritis are strongly associated with renal macrophage activation, and we envision this approach to serve as a complementary diagnostic modality to identify human glomerulonephritis.

Finally, we have several clinical studies ongoing:
1) CASTLE study (Complement Activation Signatures in Systemic Lupus Erythematosus): In collaboration with a local biotechnology company Kypha Inc., we are investigating the utility of a complement split product, iC3b, as a novel biomarker of lupus disease activity. We have a prospective, longitudinal study in our Lupus Clinic at Washington University. Our preliminary data strongly suggests that the ratio of iC3b/C3 can be predictive of active lupus disease status. We are expanding patient enrollment at WashU and recently started recruiting patients from the Mayo Clinic in collaboration with Timothy Niewold, MD.
2) SLEEPS study (Systemic Lupus Erythematosus Evaluation of Poor Sleep): Poor sleep quality has been an underappreciated issue in patients with lupus. In fact, lupus-proned mice develop lupus much earlier if they are sleep-deprived suggesting that sleep quality may play a critical role in lupus disease activity. We are prospectively collecting patient reported data and objective sleep data via actigraphy to better understand the relationship and etiologies of poor sleep quality in our lupus population.

Selected Publications:

Sinclair KC, Miner JJ, and Kim AHJ. (2015) Immunologic mechanisms of neuropsychiatric lupus. Curr Immunol Rev. In Press.

Ogdie A, Shah AA, Makris U, Jiang Y, Nelson A, Kim AHJ, Angeles-Han ST, Castelino FV, Golding A, Muscal E, Kahlenberg JM, and Bard FK. (2015) “Barriers and facilitators of a career as a physician scientists among rheumatologists in the United States.” Arthritis Care Res., doi: 10.1002/acr/22569. PMCID 25728626.

Miner JJ, Yeang HXA, Fox JM, Taffner S, Kim AHJ, Diamond MS, Lenschow DJ, and Yokoyama WM. (2015) “Brief Report: Chikungunya viral arthritis mimicking seronegative rheumatoid arthritis in a cohort of American travelers.” Arthritis Rheum. 67(5):1214-20, doi: 10.1002/art.39027. PMID: 25605621

Miner JJ, Kim AH. (2014) Cardiac manifestations of systemic lupus erythematosus.
Rheumatic Diseases Clinics of North America, 40(1):51-60. PMID: 24268009

Swiecki M, Wang Y, Riboldi E, Kim AHJ, Dzutsev A, Gilfillan S, Vermi W, Ruedl C, Trinchieri G, Colonna M. (2014) “Cell depletion in mice that express diphtheria toxin receptor under the control of SiglecH encompasses more than plasmacytoid dendritic cells.” J Immunol., 192:4409-16, doi: 10.4049/jimmunol.1303135. PMCID: PMC4194082.

Sandoval GJ, Graham DB, Gmyrek GB, Akilesh HM, Fujikawa K, Sammut B, Bhattacharya D, Srivatsan S, Kim AHJ, Shaw AS, Yang K, Bassing CH, Duncavage E, Xavier RJ, Swat W. (2013) “Novel mechanism of tumor suppression by polarity gene Discs Large1 (DLG1) revealed in a murine model of pediatric B-ALL.” Cancer Immunol Res. 1:426-37, doi: 10.1158/2326-6066.CIR-13-0065. PMCID: PMC40006353.

Yu H, Suleiman H, Kim AHJ, Miner JH, Dani A, Shaw AS, Akilesh S. (2013) “Rac1 activation in podocytes induces rapid foot process effacement and proteinuria.” Mol Cell Biol. 33:475-64, doi: 10.1128/MCB.00730-13. PMCID: PMC3838009.

Schilling JD, Machkovech HM, Kim AH, Schwendener R, Schaffer JE. (2012) Macrophages modulate cardiac function in lipotoxic cardiomyopathy. 303(11):H1366-73. PMID: 23042950 PMCID: PMC3532539

How to Identify and Interpret Genetic Contributions to Autoimmune Diseases
Kim AH.
The Rheumatology Report. 2010; 3(2).

Last Updated: 8/18/2015 8:44:34 AM

Mouse kidney cleared using a modified PACT/CLARITY approach and imaged with two-photon microscopy. In red are glomeruli (labeled with antibodies specific to nephrin), in green are collagen fibers (second harmonics), and in blue are renal tubules (second harmonics). These glomeruli are ~500 microns underneath the surface of the kidney.
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