Cell Biology and Anatomy Discipline

Center for Cancer Cell Biology, Immunology, and Infection

Dr. Kim received his PhD from the Department of Cellular and Molecular Biology, Roswell Park Cancer Institute, SUNY at Buffalo in 1999. He completed post-doctoral training at the Ernest Gallo Clinic & Research Center, UCSF, where he initiated C. elegans genetic studies. He was appointed to associate investigator, an independent researcher position, in 2006. He joined the faculty of the Chicago Medical School as an assistant professor in the summer of 2008.

Research

Every pusillanimous creature that crawls on the earth or slinks through slimy seas has a brain – from The Wizard of Oz.

Our interest aims at identifying genes essential for movement control in C. elegans (tiny worm). In particular, we use genetic and genomic approaches to understand the pathogenesis mechanisms of neurological and neuromuscular diseases.

1. The regulation of the calcium channel at the synapse. 
   Synaptic transmission is a fundamental process by which a neuron communicates with its target cell. A neurotransmitter is released from a presynaptic neuron and binds to its postsynaptic receptor on a target cell, resulting in its activation. Neurotransmitter release occurs at the active zone, a specialized structure at the presynaptic terminal. The active zone consists of a large number of proteins that coordinate the fusion of neurotransmitter-filled synaptic vesicles with the presynaptic plasma membrane. The key event that triggers the fusion of synaptic vesicles is calcium influx, which is mediated by voltage-gated CaV2 calcium channels. The abundance of CaV2 calcium channels is critical for the transmission efficacy and synaptic plasticity. However, how the abundance of CaV2 channels is regulated at synapses is understudied. How are CaV2 channels targeted to the synapse? How does synaptic activity change the abundance of CaV2 channels at synapses? We aim to address these questions by taking advantage of the genetic simplicity and amenability of C. elegans.
2. Ion channel trafficking and localization in muscles and neurons.
   Calcium ions mediate critical, essential biological processes, including synaptic transmission and muscle excitation. However, excessive calcium accumulation in the cell cause irreversible cellular damage and cell death. The BK (SLO-1) channel is a calcium-activated potassium channel that functions as a major negative feedback regulator of calcium influx and thus is known as an emergency break. Abnormal functions of BK channels are associated with a variety of disease conditions, including epilepsy, alcoholism, autism, stroke, and neurodegenerative diseases. As calcium influx is spatially and temporally limited to calcium-rich subcellular domains (e.g., presynaptic active zones and muscle excitation sites), the density and subcellular localization of BK channels have significant biological consequences. However, the mechanisms by which BK channels are trafficked and localize to these subdomains have been poorly defined. To tackles this important issue, my research group takes advantage of amenable C. elegans genetics. Thus far we have identified several novel genes that control the trafficking and/or localization of SLO-1 channels at muscle excitation sites and neuronal presynaptic terminals. Intriguingly, some of these genes are regulated by cellular stress responses such as proteasomal stress and ER-associated degradation, indicating that cellular stress responses dynamically regulate BK channel density to maintain normal calcium homeostasis.
   
   We have recently expanded how other ion channels functionally coupled with SLO-1 channels are trafficked and localize to muscles and neurons.
3. Genetic dissection of alcohol toxicity
   Chronic alcohol abuse causes the damage and toxicity to several organs, including brain, liver, and cardiac and skeletal muscles. These toxic effects of alcohol on these organs directly cause, or negatively impact, morbidity and mortality to alcohol misusers. We have found that the nematode C. elegans exhibits key features of these toxic effects when exposed to ethanol. As in humans, ethanol exposure impairs C. elegans movement, and induces the expression of genes that cope with alcohol toxicity. Particularly, we find that ethanol toxicity is centered on mitochondria, the power plants of the cell. Furthermore, we have uncovered the modulation of mitochondrial stress responses is a potentially promising therapeutic strategy to ameliorate alcohol toxicity. Using C. elegans as a model system we pursue to identify molecular mechanisms that cause the toxic effects in excitable cells, and to understand how the modulation of these mechanisms ameliorates alcohol toxicity.

For more details, please .

Publications

Xiong, A., Richmond, J.E., and Kim H. (2024). Presynaptic neurons self-tune by inversely coupling neurotransmitter release with the abundance of CaV2 voltage-gated Ca2+ channels. 

Oh, K.H.#, Xiong, A.#, Choe, J-.Y., Richmond, J.E., and Kim, H (2023). Active zone trafficking of CaV2/UNC-2 channels is independent of β/CCB-1 and α2δ/UNC-36 subunits. J. Neurosci. # co-first author 

Krout, M.D.#, Oh, K.H. #, Xiong, A., Frankel, E.B., Kurshan, P.T., Kim, H.*, and Richmond, J.E.* (2023). Clarinet/CLA-1 recruits RIMB-1/RIM-binding protein and UNC-13 to orchestrate presynaptic neurotransmitter release. Proc. Natl. Acad. Sci. U S A. 23: e2220856120 #co-first author, *co-corresponding author

Oh, K.H.^#, Xiong, A.^#, Choe, J-.Y., Richmond, J.E., and Kim, H (2023). Active zone trafficking of CaV2/UNC-2 channels is independent of β/CCB-1 and α2δ/UNC-36 subunits. J. Neurosci. # co-first author

Krout, M.D.^#, Oh, K.H. ^#, Xiong, A., Frankel, E.B., Kurshan, P.T., Kim, H.*, and Richmond, J.E.* (2023). Clarinet/CLA-1 recruits RIMB-1/RIM-binding protein and UNC-13 to orchestrate presynaptic neurotransmitter release. Proc. Natl. Acad. Sci. U S A. 23: e2220856120 #co-first author, *co-corresponding author

Oh, K.H., Krout, M., Richmeond, J.E., and Kim, H (2021). UNC-2 CaV2 channel localization at presynaptic active zones depends on UNC-10/RIM and SYD-2/Liprin-α in Caenorhabditis elegans. J. Neurosci.

Cheung, T.P., Choe, J-.Y., Richmond, J.E., and Kim, H. (2020). BK channel density is regulated by endoplasmic reticulum associated degradation and influenced by the SKN-1A/NRF1 transcription factor. PLoS Genetics, 16(6): e1008829.

Oh, K.H., Sheoran, S., Richmond, J.E., and Kim, H. (2020). Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans. FASEB J. 34(6): 8204-8216.

Oh, K.H., and Kim, H. (2019). BK channel clustering is required for normal behavioral alcohol sensitivity in C. elegans. Sci. Rep. 9(1):10224.

Oh KH, Kim H. Aldicarb-induced Paralysis Assay to Determine Defects in Synaptic Transmission in Caenorhabditis elegans. Bio Protoc. 2017 Jul 20;7(14). pii: e2400. doi: 10.21769/BioProtoc.2400. ()

Oh, K.H., Haney, J., Wang, X, Chuang, C.F., Richmond, J., and Kim, H (2017) ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans. eLife, 6:e24733. ()

Li, H, Kim, H, Furst, J., Raicu, D. (2016) A run-length encoding approach for path similarity analysis of C. elegans search behavior. Computational and Mathematical Methods in Medicine, 2016:3516089 ()

Kim, H., and Oh, K. (2016) Protein network interacting with BK channel. Int Rev Neurobiol. 2016;128:127-61. doi: 10.1016/bs.irn.2016.03.003. Epub 2016 Mar 28. ()

Moy, K., Li ,W., Tran, H.P., Simonis, V., Story, E., Brandon, C., Furst, J., Raicu, D., and Kim, H. (2015) Computational Methods for Tracking, Quantitative Assessment, and Visualization of C. elegans Locomotory Behavior. PLoS One 10(12):e0145870. ()

Truong,T., Karlinski Z.A.,, O’Hara C., Cabe, M., Kim, H., and Bakowska, J.C. (2015) Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin. PLoS One 26;10(6):e0130455. ()

Oh, K, HJ., Abraham, L., Gegg, C., Silvestri, C., Huang, Y. C., Alkema, M., Furst, J., Raicu, D., and Kim, H. (2015). Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by CaV2 calcium channels. BMC Neuroscience 16:26. ()

Oh, K, HJ., Kim, H. (2013). IGF signaling in muscle degenerative diseases. Aging. 5(12):865-6. ()

Oh, K, HJ., Kim, H. (2013). Reduced IGF signaling prevents muscle cell death in a Caenorhabditis elegans model of muscular dystrophy. Proc. Natl. Acad. Sci. U S A. 110(47):19024-9. ()

Metzler, R., Meleshkevitch, E.A., Fox, J., Kim, H., and Boudko, D.Y. (2013) A SLC6 transporter of the novel B0,- system aids in absorption and detection of nutrient amino acids in Caenorhabditis elegans. J. Exp Biol., 216(Pt 15):2843-57. ()

Oh, H. J., Abraham, L. S., van Hengel, J., Stove, C., Proszynski, T.J., Gevaert, C., DiMario, J.X., Sanes, J. R., van Roy F, and Kim, H. (2012) The interaction of of alpha-catulin with dystrobrevin contributes to the integrity of the dystrophin complex in muscle. J. Biol. Chem., 287:21717-21728. ()

Sancar F., Touroutine D., Gao S., Oh H. J., Gendrel M., Bessereau J.-L., Kim H., Zhen M., and Richmond J. E. (2011). The dystrophin-associated protein complex maintains muscle excitability by regulating BK channel localization. J. Biol. Chem., 286:33501-33510. ()

Abraham, L. S., Oh, H. J., Sancar, F., Richmond, J. E., and Kim, H. (2010). An alpha-catulin homologue controls neuromuscular function through localization of the dystrophin complex and BK channels in Caenorhabditis elegans. PLoS Genetics, 6(8): e1001077. ()

*Kim, H., Pierce-Shimomura, J. T., Oh, H. J., Johnson, B. E., Goodman, M. B., and *McIntire, S. M. (2009). The dystrophin complex controls BK channel localization and muscle activity in Caenorhabditis elegans. PLoS Genetics, 5(12): e1000780. *Co-corresponding author ()

Kim, H., Rogers, M. J., Richmond, J. E., and McIntire, S. M. (2004). SNF-6 is an acetylcholine transporter interacting with the dystrophin complex in Caenorhabditis elegans. Nature, 430, 891-896. ()

Davies, A. G., Shimomura-Pierce, J. T., Kim, H., VanHoven, M. K, Thiele, T. R. Bonci, A., Bargmann, C. I. and McIntire, S. M. (2003). A central role of BK channel in behavioral responses to ethanol in C. elegans. Cell, 115, 655-666. ()

Articles (1995-1999)

Kim, H., and Baumann, H. (1999). Dual signaling role of protein tyrosine phosphatase SHP-2 in regulating expression of acute phase plasma proteins by IL-6 type cytokine receptors in hepatic cells. Mol. Cell. Biol. 19, 5326-5338. ()

Lai, C.F., Ripperger, J., Wang, Y., Kim, H., Hawley R. B., Baumann H. (1999). The STAT3-independent signaling pathway by glycoprotein 130 in hepatic cells. J. Biol. Chem. 274, 7793-802. ()

Lim, S.-K., Kim, H., Lim, S. K., bin Ali, A., Lim, Y. K., Wang, Y., Chong, S. M., Costantini, F., and Baumman, H. (1998). Increased susceptibility in Hp knockout mice during acute hemolysis. Blood 92, 1870-1877. ()

Kim, H., Hawley, T., Hawley, R., and Baumann, H. (1998). Protein tyrosine phosphatase (SHP-2) moderates signaling by gp130 but is not required for the induction of acute-phase plasma protein genes in hepatic cells. Mol. Cell. Biol. 18,1525-1533. ()

Kim, H., and Baumann, H. (1997). Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells. J. Biol. Chem. 272, 30741-30747. ()

Kim, H., and Baumann, H. (1997). The carboxyl-terminal region of STAT3 controls gene induction by the mouse haptoglobin promoter. J. Biol. Chem. 272,14571-14579. ()

Baumann, H., Morella K. K., White, D. W., Dembski, M., Bailon, P. S., Kim, H., Lai, C. F., and Tartaglia, L. A. (1996). The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. in U. S. A. 93,8374-8378. ()

Kim, H., Lee, H., S., Chang, K., T., Ko, T., H., Baek, K., J., and Kwon, N., S. (1995). Chloromethyl ketones block induction of nitric oxide synthase in murine macrophages by preventing activation of nuclear factor-kappa B. J. Immunol. 154, 4741-4748. ()

Lab

We are often looking for new undergraduate, graduate and medical students. We have several research projects fit to the various levels of research experience. Inquiries into research opportunities are welcome.

Current members

Kelly Oh (Research Assistant Professor)
Tim Cheung (Graduate /DPM student)
Ana Andrea Adam (Research Assistant)

Former members

Linu Abraham (Post-doc)
James Haney (Undergraduate, Lake Forest College)
Christian Silvestri (Undergraduate, Lake Forest College)