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Kim Lab

key processes flowchartOne of the key processes in energy balance is to sense and respond to changes in nutrients (e.g amino acids, glucose, or lipid). How do nutrient sensors converge to control appetite and energy balance?

Energy Homeostasis, Food Intake, Obesity, and Metabolic Syndrome

The ability to sense nutrients and regulate energy balance is a fundamental process of all the living creatures. Obesity, an increasingly common health problem in the U.S. and throughout the developed world, has been acknowledged as the second leading cause of death, behind smoking. Obesity has been linked to diabetes, hypertension, cardiovascular disease, cancer, and a myriad of other health problems. Obesity results from disturbed energy balance, where energy intake (i.e. feeding) chronically exceeds total energy expenditure. A flurry of research activities has identified many genetic or biochemical components for nutrient sensing and has elucidated their roles in obesity and obesity-associated diseases. However the mechanism(s) underlying the development of obesity and the interplay between numerous components are still poorly understood. One of the primary goals in my laboratory is to understand how our body senses and responds to different levels of nutrients such as glucose or lipid, and how different pathways cross talk to each other.

 

Projects

flowchart
Chart of synaptic pathologySynaptic "pathology" due to subchronic High Fat Diet (HFD). Hippocampal sections from normal chow and HFD-fed mice, immunolabeled for postsynaptic and presynaptic enriched proteins. (Arnold et al, Neurobiology of Diseases, 2014)

Obesity is a major public health problem that affects approximately 30% of US adults. There is a growing body of evidence supporting the idea that obesity-induced metabolic stress is associated with significant neural and cognitive deficits in addition to its negative impacts on the rest of body, and that these cognitive deficits often increase with age.

SREBP in postmortem brain from Schizophrenia patientsSREBP (a master regulator of lipid synthesis) in postmortem brain from Schizophrenia patients. SREBP protein level is extremely reduced in Schizophrenia patient brain. (Yong et al, Mol Neuro, 2016)

We previously demonstrated that metabolic stressors induced by obesity lead to similar biochemical, morphological, electrophysiological and behavioral phenotypes as those seen in animal models of dementia or Alzheimer’s disease (AD).

Moreover, we have shown that these phenotypic changes are associated with the loss of inositol polyphosphate multikinase (IPMK) in the cortex and hippocampus, suggesting that the loss of this nutrient sensing protein contributes to these phenotypes.

One of the long-term objectives of this laboratory is to determine the cellular underpinnings of metabolic stress-induced cognitive dysfunction, with the ultimate goal of developing novel interventions.

Other relevant projects include:

  1. The role of the inositol pathway in energy metabolism.
  2. The effects of metabolic imbalance on neuronal function and various neuropsychiatric conditions
  3. The role of CNS (central nerve system) metabolic genes on affective disorders.
  4. The effects of atypical antipsychotic drugs on metabolic imbalance
  5. The role of lipid pathways on oligodendrocyte differentiation
 

Our Team

Sangwon Kim

Sangwon Kim, Ph.D.
Principal Investigator
Email: skim132@jhmi.edu
Office: 410-550-6200

Becky Tu-Sekine

Becky Tu-Sekine, Ph.D.
Senior Research Specialist
Email: btusekine@jhmi.edu
Office: 410-550-6283

Jiny Kim

Jiny Kim
Research Fellow

 

Publications

The following is a selected list of publications. Please visit PubMed for a complete list of publications.

  1.  Brynildsen JK, Lee BG, Perron IJ, Jin S, Kim SF, Blendy JA.: Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal. Proc Natl Acad Sci U S A. 2018 Apr 2. pii: 201707047. doi: 10.1073/pnas.1707047115. [Epub ahead of print]
  2. Chen Y, Bang S, McMullen MF, Kazi H, Talbot K, Ho MX, Carlson G, Arnold SE, Ong WY, Kim SF: Neuronal activity induced sterol regulatory element binding protein-1 (SREBP) is disrupted in dysbindin null lice-Potential link to cognitive impairment in schizophrenia. Molecular Neurobiology 54(3): 1699-1709, April 2016
  3. Monnerie H, Romer M, Jensen BK, Millar JS, Jordan-Sciutto KL, Kim SF, Grinspan JB: Reduced Sterol Regulatory Element-Binding Protein (SREBP) Processing Through Site-1 Protease (S1P) inhibition Alters Oligodendrocyte Differentiation in vitro. Journal of Neurochemistry 140(1): 53-67, January 2017
  4. Chen Y, Bang S, Shi H, Park S, Kim SF: Acyl-CoA Binding Domain Containing 3 Modulates NAD+ Metabolism through Activating Poly(ADP-ribose) Polymerase 1.; Lipid pathway modulates PARP1. Biochemical Journal 469(2): 189-198, May 2015.
  5. Yarchoan M, Talbot K, Toledo JB, Lee EB, Arvanitakis Z, Kazi H, Han LY, Lee VM-Y, Kim SF, Trojanowski J, Arnold SE: Abnormal serine phosphorylation of insulin receptor substrate-1 is associated with tau pathology in Alzheimer's disease and tauopathies. Acta Neuropathologica 128(5): 679-689, November 2014.
  6. Arnold SE, Lucki I, Brookshire BR, Carlson GC, Browne CA, Kazi H, Bang S, Choi BR, Chen Y, McMullen MF, Kim SF: High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice. Neurobiology of Disease 67: 79-87, 2014.
  7. Bang S, Chen Y, Ahima RS, Kim SF: Convergence of IPMK and LKB1/AMPK signaling pathways on metformin action. Molecular Endocrinology 28(7): 1186-1193, 2014.
  8. Yarchoan M, Talbot K, Toledo JB, Lee EB, Arvanitakis Z, Kazi H, Han LY, Lee VM-Y, Kim SF, Trojanowski J, Arnold SE: Abnormal serine phosphorylation of insulin receptor substrate-1 is associated with tau pathology in Alzheimer's disease and tauopathies. Acta Neuropathologica 128(5): 679-689, November 2014.
  9. Teff K, Kim SF: Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism. Physiology and Behavior 104(4): 590-598, Sep 2011. Kim SF: Animal models of eating disorders. Neuroscience 211: 2-12, 2012.
  10. Bang S, Kim, S., Dailey MJ, Chen Y, Moran TH, Snyder SH, Kim, SF: AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase. The Proceedings of the National Academy of Sciences in the United States of America 109(2): 616-620, 2012.
  11. Chen Y, Patel V, Bang S, Cohen N, Millar J, Kim SF: Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3. Public Library of Science One 7(11): e49906, 2012.
  12. Kim S*, Kim SF*, Maag D, Maxwell MJ, Resnick AC, Juluri KR, Chakraborty A, Koldobskiy MA, Cha SH, Barrow R, Snowman AM, Snyder SH: Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase. Cell Metabolism 13(2): 215-221, 2011 Notes: *(Co-first author).
  13. Kim SF, Huang AS, Snowman AM, Teuscher C, Snyder SH: From the Cover: Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proceedings of the National Academy of Sciences of the United States of America 104(9): 3456-3459, Feb 27 2007.
 

Opportunities in Dr. Kim's Lab

Graduate Students

Several rotation projects are available in the lab. Please see the home page for the details of our experimental systems and techniques. Graduate students are encouraged to participate in the experimental design,  technical training and support from the Principal Investigator (PI)  and experienced lab members will always be available. Interested students are welcome to contact the PI to discuss the potential projects.

Medical Students and Undergraduate Students

We also welcome medical and undergraduate students from Johns Hopkins University as well as other schools to carry out research projects (e.g. summer project, thesis project, etc...) in our laboratory, please contact the PI for more information.

Research Fellows

To apply for a postdoctoral position in the lab, please send a cover letter including your research interest, your CV, and the names of three references to the PI.

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