Faculty

Pioneering Rehabilitation

Sunghee Cho, Ph.D.

Director, Preclinical Stroke Modeling

Associate Professor
Brain and Mind Research Institute
Weill Cornell Medical College

Phone:

(914) 597-2162

Research Focus

Although stroke is a primary cause of disability and death in the U.S., few options exist for treating patients who have had a stroke. The paucity of treatment options has prompted the field to focus on identification and validation of potential targets for developing treatment strategies. Focused on preclinical stroke studies on in vivo pathology, my lab closely examines stroke pathology and addresses a gap between preclinical and clinical settings for translational medicine.

Two main lines of research have been established in my laboratory; acute pathology/neuroprotection and long-term stroke recovery. For the former, we has been examined several well known risk factors associated with higher incidence of vascular diseases including hypercholesterolemia, diabetes, and obesity, and systematically examined their effect on stroke outcome in experimental animal models of stroke. In addition, close examination of stroke pathology revealed involvement of multiple-pro-death processes including inflammation, apoptosis, oxidative stress, and vascular dysfunction. Thus, targeting a specific pathway may not overcome the heterogeneous nature of stroke pathology. This led to the concept of a multi-modal approach: targeting a molecule that is involved in multiple pathogenesis, thereby simultaneously mitigating pro-death pathways. To this end, we proposed that CD36, a class B scavenger receptor, is a potential target molecule for a multi-modal approach. We have been particularly focuses on in vivo phenomena and the underlying events by which peripheral inflammatory status influences the acute outcome of stroke-induced injury through a novel CD36 mechanism.

Equally important are the strategies that promote functional recovery. Currently, improvements in care for the acute stroke patient have resulted in reduced stroke mortality, leaving more survivors with severe disability. However, treatments that reduce post-stroke impairment are limited. To this end, we have studied a role of brain-derived neurotrophic factor (BDNF), a widely expressed neurotrophin that plays a critical role in stroke recovery. Recently, a single nucleotide polymorphism (SNP) in the prodomain of bdnf that leads to substitution of methionine (met) for valine (val) at codon 66 (val66Met) has been identified. This variant, found only in humans, occurs with a frequency of 20-30% in Caucasians and up to 70% in Japanese and Chinese populations. The discovery of the common genetic variant of BDNF in human population provides an interesting research focus that leads to evaluate a potential role of BDNF-mediated angiogenesis/synaptogenesis on stroke outcome and recovery. By utilizing mice with genetic knock-in of the humanized bdnf variant in both alleles (BDNFMet/Met) and wild type (BDNFVal/Val), my lab has been addressing the mechanisms by which BDNF contributes to stroke recovery. The proposed mechanistic and functional studies may potentially lead to translational approaches that aim at reversing a BDNF secretion deficit and downstream pathways to promote reparative processes for stroke patients with SNP. Furthermore, increased CD36 in BDNF SNP carrier led an interesting overlap between peripheral immunity via CD36 and genetics of stroke recovery. Our research will focus on the pathology and repair mechanisms throughout different stroke stages (i.e., prevention, acute, sub-acute, and recovery phases). By manipulating the CD36 axis using CD36 antagonist(s) and agonist(s) in normal and BDNF SNP carriers, our next phase of study will be on stroke-stage specific targeting CD36 to facilitate pharmacological interventions.

Biography

Sunghee Cho received her BS in Chemistry at Yonsei University in Korea and MS in Nutrition at Cornell University. In 1993, she received her Ph.D at the Department of Neurology/Neuroscience from Weill Cornell Medical College. She continued a post-doctoral fellowship at the laboratory of Molecular Neurobiology under the mentorship of Dr. Tong Joh and appointed for first faculty position as an instructor at Burke Medical Research Institute at Weill Cornell Medial College and an assistant professor in the Department of Neurology/Neuroscience at Weill Cornell Medical College. She is currently an associate professor in the Brain Mind Research Institute at Weill Cornell Medical College and a director of Preclinical Stroke Modeling at Burke Medical Research Institute. She is an editorial member of Stroke, Cerebral Blood Flow/Metabolism, and Translational Stroke Research and Fellow of American Heart/Stroke Association (FAHA), Council member on Stroke. She is a chartered NIH neural oxidative metabolism and death (NOMD) study section member and recently served a US representative of National Institute Neurological Disorder and Stroke (NINDS, NIH) in participating European Multi-preclinical Animal Research Team Network Consortium.

Cho Laboratory focuses on the neuron-immune interaction in stroke-induced brain injury and stroke repair mechanism. The studies are funded through NINDS, NHLBI, NCRR at National Institute Health, American Heart Association, Sanofi, and Burke foundation.

B.S. Chemistry
Yonsei University, Seoul Korea

M.S. Human Nutrition
Cornell University, USA

Ph.D Neuroscience
Weill Cornell Medical College, USA

Postdoctoral Fellowship
Weill Cornell Medical College, USA

Instructor
Weill Cornell Medical College, USA

Assistant Professor
Burke/Cornell Medical Research Institute, USA
Weill Cornell Medical College, USA

Publications

Citations via Google Scholar | PubMed


Publications

Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR (2016) Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models Sci Transl Med 2016 Mar;8(328):328ra29 PMID: 26936506

Kim E, Woo M, Qin L, Ma T, Beltran C, Bao Y, Bailey JA, Corbett D, Ratan RR, Lahiri DK, Cho S (2015) Daidzein augments cholesterol homeostasis via ApoE to promote functional recovery in chronic stroke. J Neuroscience 35:15113-26 PMCID: PMC4642242

Kim E, Tolhurst AT, Szeto HH, Cho S (2014) Targeting CD36-Mediated Inflammation Reduces Acute Brain Injury in Transient, but not Permanent, Ischemic Stroke. CNS Neurosci Ther Apr;21(4):385-91. doi: 10.1111/cns.12326. PMCID:PMC4362808

Kim E, Yang J, Beltran C, Cho S (2014) Role of spleen-derived monocoytes/ macrophages in acute ischemic brain injury. J Cereb Blood Flow Metab 34(8):1411-9 PMCID: PMC4126087

Kim E, Tolhurst A, Cho S (2014) Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury. J Neuroinflammation 11(1):83. doi: 10.1186/1742-2094-11-83 PMCID: PMC4017808

Qin L, Jing D, Parauda S, Carmel J, Ratan R, Lee F, Cho S (2014) An Adaptive Role for BDNF Val66Met Polymorphism in Motor Recovery in Chronic Stroke. J Neuroscience 34(7):2493-502 PMCID: PMC392142.

Qin L, Jing D, Parauda S, Carmel J, Ratan R, Lee F, Cho S (2014) BDNF Met allele promotes stroke recovery via contralateral striatal plasticity J Neuroscience 34(7):2493-502 PMCID: PMC3921423

Cho S, Febbraio M. (2013) CD36: An Inflammatory Mediator in Acute Brain Injury. In Immunological Mechanisms and Therapies in Brain Injury and Stroke. Springer, 2013 321-347

Yu Chen, Hengchang Guo, Wei Gong, Luye Qin, Hossein Aleyasin, Rajiv R Ratan, Sunghee Cho, Jianxin Chen, and ShusenXie (2013) Recent Advances in Two-Photon Imaging: Technology Developments and Biomedical Applications. Chinese Optics Letters Vol. 11(1), 011703 

Kim E, Febbraio M, Bao Y, Tolhurst AT, Epstein JF, Cho S (2012) CD36 in the periphery and brain synergizes in stroke injury in hyperlipidemia. Annals of Neurology 71(6):753-64 PMCID: PMC3383818

Bao Y, Wang L, Xu Y, Yang Y, Wang L, Si S, Cho S*, Hong B*. (2012) Salvianolic acid B inhibits macrophage uptake of modified low density lipoprotein (mLDL) in a scavenger receptor CD36-dependent manner. Atherosclerosis 223(1):152-9 (*co-corresponding authors) PMCID: PMC3389144

Cho S. (2012) CD36 as a therapeutic target for endothelial dysfunction in stroke. Current Pharmaceutical Design 18(25):3721-30 PMCID: PMC3411860

Bao Y, Qin L, Kim E, Bhosle S, Guo H, Febbraio M, Haskew-Layton RE, Ratan R, Cho S. (2012) CD36 is involved in astrocyte activation and astroglial scar formation. J Cereb Blood Flow Metab 32(8):1567-77 PMCID: PMC3421096

Zhou P, Qian L, D’Aurelio M, Cho S, Wang G, Manfredi G, Pickel V, Iadecola C. (2012) Prohibitin reduces mitochondrial free radical production and protects brain cells from different injury modalities. J Neuroscience 32:583-92 PMCID: PMC3287080

Park L, Wang G, Zhou P, Zhou J, Pitstic R, Previti M, Younkin Lm YounkinS, van Nostrand W, Cho S, Anrather J, Carlson G, Iadecola C. (2011) Scavenger receptor CD36 is essential for the cerebrovascular oxidative stress and neurovascular dysfunction induced by amyloid-β. Proc Natl Acad Sci 108(12):5063-8 PMCID:PMC3064396

Qin L, Kim E, Ratan R, Lee F, Cho S. (2011) Genetic variant of BDNF (Val66Met) SNP attenuates stroke-induced angiogenic responses by enhancing CD36 expression. J Neuroscience 31(2):775-783 PMCID: PMC3308129

Bao Y, Kim E, Bhosle S, Mehta H, Cho S. (2010) A role for spleen monocytes in post-ischemic brain inflammation and injury. J Neuroinflammation 7:92. PMCID:PMC3016273

Cho S, Kim E. (2009) CD36: A multi-modal target for acute stroke therapy. J Neurochemistry 1:126-132 PMCID: PMC2702148

Shin JA, Park E-M, Choi J-S, Seo S-M, Lee J, Kang L, Lee K-E, Cho S. (2009) Ischemic preconditioning-induced neuroprotection is associated with differential expression of IL-1β and IL-1 receptor antagonist in the ischemic cortex. J Neuroimmunology 217:14-19 PMCID:PMC2916648

Kim E, Tolhurst AT, Qin LY, Chen XY, Febbraio M, Cho S. (2008) CD36/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury. J Neuroscience30;28(18):4661-70 PMCID: PMC2830708

Langley B, D'Annibale MA, Suh K, Ayoub I, Tolhurst A, Bastan B, Yang L, Ko B, Fisher M, Cho S, Beal MF, Ratan RR. (2008) Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection. J Neuroscience 2;28(1):163-76 PMCID: PMC2577229

Cho S*, Szeto H.H., Kim E., Kim H., Tolhurst A.T., Pinto T.P. (2007) A novel cell permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. J Biol Chem 282(7):4634-4642 (*corresponding author)

Kawano T, Anrather J., Zhou P, Park L, Wang G, Frys K, KunzA, Cho S, Oria M, Iadecola C. (2006) Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Nature Medicine 12(2):1-5

Park E-M, Cho S, Frys K, Glickstein S, Zhou P, Anrather J, Ross, M. E, Iadecola C. (2006) Inducible nitric oxide synthase contributes to gender differences in ischemic brain injury. J Cereb Blood Flow Metab 26:392-401

Park E-M, Cho S. (2006) Enhanced ERK-dependent CREB activation reduces apoptosis in staurosporine treated human neuroblastoma SK-N-BE(2)C cells. Neuroscience Letter 402:190-4

Cho S, Park E-M, Febbraio M, Anrather J, Park L, Racchumi G. Silverstein R, Iadecola, C. (2005) A class B scavenger receptor CD36 mediates free radical production and tissue injury in cerebral ischemia. J Neuroscience 25:2504-2512

Park E-M, Cho BP, Volpe BT, Cruz MO, Joh TH, Cho S. (2005) Ibuprofen protects ischemia-induced neuronal injury via up-regulating IL-1ra expression. Neuroscience 132:625-631

Cho S, Park E-M, Zhou P, Frys K, Ross EM, Iadecola C. (2005) Obligatory role of inducible nitric oxide synthase in ischemic preconditioning. J Cereb Blood Flow Metab 25:493-501

Iadecola, C., Cho S, G. Feuerstein, and J. Hallenbeck. (2004) Cerebral Ischemia and Inflammation. In Stroke: Pathophysiology, Diagnosis, and Management, 4th ed J. P. Moore, D. Choi, J.C. Grotta, B. Weir and P.A. Wolf, Eds. Churchill Livingstone, NY, 883-894

Funding

National Institute of Health
National Heart Lund and Blood Institute
BR01 HL082511
This proposal addresses the mechanism(s) by which peripheral immunity is regulated by cerebral ischemia and how this contributes to CNS damage in acute stroke through a novel CD36 mechanism.
Dates: 8/5/2006-12/31/2015
Role: Principal Investigator - Sunghee Cho, Ph.D.

National Institute of Health
National Institute of Neurological Disorders and Stroke
R01 NS095359-10
This proposal addresses the mechanism(s) by which peripheral immunity regulated by CD36 contributes to functional recovery in chronic stroke.
Dates: 9/30/2015-8/31/2020
Role: Principal Investigator - Sunghee Cho, Ph.D.

National Institute of Health
National Institute of Neurological Disorders and Stroke
R01 NS077897
The award is to investigate the impact of BDNF polymorphism on stroke recovery and motor function.
Dates: 12/01/2012-11/31/2017
Role: Principal Investigator - Sunghee Cho, Ph.D.

Sanofi iAward
This award investigate the effect of CD36 inhibition to control visceral obesity/insulin resistance in BDNF val66met carrier
Dates: 12/15/2015-12/15/2016
Role: Principal Investigator - Sunghee Cho, Ph.D.

Burke Foundation
The support is to run stroke modeling core facility at Burke Medical Research Institute.
Dates: 2004-2016
Role: Principal Investigator - Sunghee Cho, Ph.D.

American Heart Association
Postdoctoral fellowship award
The proposal address the effect of post-stroke limb conditioning on monocyte/macrophage subsets and stroke recovery.
Dates: 07/2015-06/2017
Roles: Principal Investigator - Jiwon Yang, Ph.D.; Mentor - Sunghee Cho, Ph.D.

National Research Foundation of Korea
Postdoctoral fellowship award
The award addresses stroke therapy through macrophagic immune modulation in stroke model
Dates: 11/2013-10/2014
Roles: Principal Investigator - Jiwon Yang, Ph.D.; Mentor - Sunghee Cho, Ph.D.

Current Projects

The role of CD36 in stroke-induced inflammation and brain injury

Stroke-induced brain injury has been viewed mainly from a neurocentric perspective, with much attention given to the primary injury site and its penumbra. However, an important notion derived from recent studies, including our own, favor a view that the peripheral inflammatory state influences the outcome of primary injury. We investigate the mechanism(s) by which peripheral immunity may be regulated by cerebral ischemia and how this contributes to CNS damage in stroke. Despite a well-documented role of CD36 in the pathogenesis of other conditions such as atherosclerosis, inflammation, and lipid metabolism, its role in cerebral ischemic injury had not been delineated. We believe that our report on CD36 is the first study that demonstrates the role of this receptor in inflammation and brain injury in ischemic stroke. As CD36 is expressed in many different tissues and cell types, including peripheral monocytes/macrophages, our studies focus on the effect of CD36 expressed in the peripheral organs including bone marrow, spleen and blood. Major findings from these studies are the recognition of peripheral immunity on CNS injury, validating CD36 as a target in acute pathology, and characterizing a pharmacological agent that inhibits CD36 pathways. This ongoing project is to identify novel molecular targets that may serve as possible therapeutic strategies to attenuate acute stroke pathology. Relevant publications to this project are:

Comorbid-modified inflammation and brain injury in stroke

The recurring failure to translate neuroprotective strategies in animal models into clinical settings prompted us to reevaluate existing preclinical stroke models. One major issue in preclinical studies has been the lack of inclusion of prevalent risk factors in animal models of stroke. We have been addressing this issue by including hyperlipidemia and diabetes, prevalent co-morbid conditions, in our experimental model of stroke. We reported that animals with these risk factors displayed increased peripheral inflammation and resulted in exacerbation of ischemic brain injury. Our contributions from these studies to the stroke field are the demonstration of comorbidity-modified inflammation and injury in ischemic stroke. Relevant publications are:

Genetics of Stroke recovery: Impact of BDNF SNP on plasticity and motor function

Because strategies that promote acute neuroprotection have not successfully translated into clinical practice, studies to understand repair/recovery mechanisms that promote functional recovery have emerged. Genetics is among several factors that influence stroke recovery. We have studied the role of the BDNF single nucleotide polymorphism (SNP) on stroke recovery. The BDNF SNP is common in humans. However, carrying the BDNF SNP has been negatively associated with stroke outcome and recovery. Addressing the impact of the BDNF SNP on stroke recovery in mice that have the human BDNF SNP, we provided important evidence that BDNF SNP mice displayed better recovery through structural and molecular plasticity in the contralateral hemisphere. The contribution of our genetics of stroke recovery studies is to provide rigorous preclinical long-term stroke recovery model that has 6-month post-stroke longitudinal behavior measurement. This ongoing project will provide insight into predicting the course of stroke recovery in subjects that carry the BDNF SNP. Published reports relevant to this project are:

Presentations

October 2015
Symposium
Symposium Speaker, Novel applications of FDA approved drugs in neurological rehabilitation
American Society of Neural Rehabilitation 2015, Chicago IL

October 2015
Invited Talk
Departments of Neuroscience, Cleveland Clinics Lerner Research Institute, Cleveland OH

June 2015
Abstract Presented
Jiwon Yang, Cesar Beltran and Sunghee Cho
Post-stroke Limb Conditioning Induced Benefits Occur Through Modulating Peripheral Immunity
Cerebral blood flow and metabolism, Brain 2015, Vancouver Canada

June 2015
Abstract Presented
Eunhee Kim, Moon-Sook Woo, Luye Qin, Cesar D Beltran, Dale Corbett, Debomoy K Lahiri, Rajiv R Ratan and Sunghee Cho
Daidzein augments ApoE to promote recovery of motor function following ischemic stroke in mice
Cerebral blood flow and metabolism, Brain 2015, Vancouver Canada

February 2015
Presentation
Moderator, Basic and preclinical neuroscience of stroke recovery, oral abstract session
International Stoke Conference 2015, Nashville, TN

February 2015
Abstract Presented
Jiwon Yang and Sunghee Cho
Post-stroke Body Weight Loss Predicts Acute Stroke Outcome In Mice
International Stroke Conference 2015

Laboratory

Current Lab Members

Eunhee Kim, Ph.D
Instructor
Euk2004@med.cornell.edu

Moonsook Woo, Ph.D
Postdoctoral Fellow
Mow3001@med.cornell.edu

Jiwon Yang, Ph.D.
Postdoctoral Fellow
Jiy3001@med.cornell.edu

Cesar Beltran, B.S.
Research Assistant
Ceb3001@med.cornell.edu