Jung-Whan Kim

Assistant Professor, Biological Sciences
Co-Director, Small Animal Imaging Core Facility
jay.kim@utdallas.edu
972-883-3502
BSB12.530
Jay Kim Lab
ORCID
Tags: Molecular Biology Cell Biology Cancer Metabolism Tumor Microenvironment Hypoxia Fibrosis Biology Biochemistry and Biophysics Pathobiology

Professional Preparation

Ph.D. - Cancer Biology
Johns Hopkins School of Medicine - 2006
D.V.M. - Veterinary Medicine
KonKuk University, Korea - 2000

Research Areas

Jay Kim lab is focused on understanding the heterogeneous metabolic signatures and targetable vulnerabilities in squamous cell carcinoma utilizing genetically engineered mouse models (GEMMs) and patient-derived xenograft (PDX) systems. Another major focus of our research is to understand the significance of hypoxic signaling and metabolic reprogramming of fibroblasts in cancer progression and fibrotic diseases.

Publications

A new perspective on the heterogeneity of cancer glycolysis 2018 - Journal Article
Convergence of cancer metabolism and immunity: An overview 2018 - Journal Article
Glucose Transporter 1 Gene Variants Predict the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer 2018 - Journal Article
Regulation of acetate utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC) 2018 - Journal Article
Spatial Angular Compounding Technique for H-Scan Ultrasound Imaging 2018 - Journal Article
Targeting hypoxia-inducible factor-1a/pyruvate dehydrogenase kinase 1 axis by dichloroacetate suppresses bleomycin-induced pulmonary fibrosis 2018 - Journal Article
18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma 2017 - Journal Article
Erratum: MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer (Cancer Cell (2017) 32(1) (71–87.e7) (S1535610817302544) (10.1016/j.ccell.2017.06.004)) 2017 - Journal Article
Lung squamous cell carcinoma exhibits a targetable glucose dependency unique among non-small cell lung cancers 2017 - Journal Article
MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer 2017 - Journal Article

Appointments

Assistant Professor
University of Texas at Dallas [2013–Present]
Postdoctoral Fellow
University of California San Diego / Salk Institute [2008–2013]
Research Fellow
University of Pennsylvania [2000–2002]

Awards

Lung Cancer Discovery Award - American Lung Association [2016]
I M Rosenzweig Young Investigator Award - Pulmonary Fibrosis Foundation [2014]
Symposia Scholarship - Keystone Symposia [2012]
NRSA F32 Post-doctoral Fellowship - NIH/NCI [2011]
NRSA T32 Post-doctoral Fellowship - NIH/NCI [2010]
Symposia Scholarship - Keystone Symposia [2006]
Pathology Young Investigator Award - Johns Hopkins School of Medicine [2004]
Pre-doctoral Fellowship - Howard Hughes Medical Institute (HHMI) [2003]

Projects

Elucidating and Targeting the Glycolytic Reliance of Lung Squamous Cell Carcinoma
Lung cancer is a leading cause of cancer related death and has a higher mortality rate than colorectal, breast, and prostate cancers combined. Lung squamous cell carcinoma (SqCC), a subtype of lung cancer, accounts for 25-30% of all lung cancers. Although much research into lung cancer and possible treatments are being investigated, lung SqCC has benefited very little from the application of targeted therapeutic options, as a result, decades old platinum-based chemotherapy regiments remain the first-line treatment options. Therefore, identification of targetable vulnerabilities in lung SqCC is imperative to improve therapeutic outcome of lung SqCC patients.  There is an increasing body of evidence arguing for substantial heterogeneity in how individual cancers utilize glucose in promoting tumorigenesis. We recently reported that lung SqCC exhibits distinctively elevated GLUT1 expression resulting in high susceptibility to glycolytic inhibition whereas lung adenocarcinoma (ADC) is significantly less reliant on glucose and thereby resistant to glycolytic inhibition. Our group is focused on elucidating the molecular mechanisms underlying this previously unrecognized GLUT1-mediated glucose metabolism in lung squamous cancers. Targeting cancer glycolysis, on the assumption that glycolytic metabolism is uniformly elevated in most human cancers, has proven to be clinically unsatisfactory. Our discovery of distinct and exceptional glycolytic signature and glucose reliance phenotypically linked to lung SqCC argue that lung SqCC can be uniquely vulnerable to glucose restriction.
Tumor-associated Stromal Cells within the Hypoxic Tumor Microenvironment
The tumor microenvironment is comprised of host stromal cells, soluble growth factors and extracellular matrix that plays a critical role for virtually all tumorigenic processes. Tumor-associated stromal alterations are integral components of the tumor microenvironment that contribute to tumor growth and progression. Among many cellular populations, stromal fibroblasts are prominent cell populations of the tumor microenvironment and have been implicated in the development of various cancers including breast and pancreatic cancers. Unlike stromal cells residing in normal tissue, tumor-associated fibroblasts exhibit distinctive tumor-promoting features: they contribute to tumor cell proliferation, inflammation, angiogenesis, invasion and metastatic dissemination.​​In particular, my laboratory is interested in the mechanisms underlying the effects of stromal hypoxic signaling in tumorigenesis, angiogenesis and remodeling of the tumor microenvironment. The remodeling response to hypoxia is controlled primarily by hypoxia-inducible transcription factors (HIFs) 1 and 2, and the negative regulator of HIFs, von Hippel Lindau protein (VHL). We employ transgenic animal models in which the hypoxic response has been genetically ablated via deletion of VHL, HIFs and their target genes in various stromal components including fibroblasts in various tumor models to better understand the relationship of tumor-associated fibroblasts to tumor progression in the context of the hypoxic tumor microenvironment.
Metabolic Targeting of Fibrotic Diseases
Pulmonary fibrosis, scarring of the lungs caused by many conditions such as infections, environmental agents, and certain medications, is a ultimately fatal progressive disease with not only limited treatment options but also a poor prognosis and a survival expectancy of less than five years. Furthermore, idiopathic pulmonary fibrosis, the most common form of the disease, has no known cause. Therefore, it is crucial that mechanisms underlying pulmonary fibrosis progression be elucidated.​The presence of myofibroblasts in the animal models of pulmonary fibrosis as well as patients with lung fibrosis has been well documented in the current literature. Furthermore, myofibroblasts, which are responsible for the deposition of the matrix that constitutes the scar, have been found to play integral roles in the pathogenesis of this disease. During fibrotic progression, myofibroblast differentiation of pulmonary fibroblasts is a major process that facilitates the progression, migration, and secretion of extracellular matrix and collagen. In my lab, we are currently investigating the glycolytic reprogramming of fibroblasts that is crucial in fibroblast to myofibroblast differentiation utilizing in vitro culture as well as animal models in order to identify novel therapeutic targets.

News Articles

Biologists’ Preclinical Work Suggests Keto Diet Has Anti-Cancer Effect
It’s well known that keeping blood glucose levels in check can help individuals avoid or manage diabetes, but new research led by biologists at The University of Texas at Dallas suggests that restricting blood glucose levels might also keep certain cancers at bay.

In a study published online Aug. 13 in the journal Cell Reports, researchers restricted circulating glucose in mice with lung cancer. Circulating glucose restriction was achieved by feeding the mice a ketogenic diet, which is very low in sugar, and by giving them a diabetes drug that prevents glucose in the blood from being reabsorbed by the kidneys.

Activities

Journal Editorial Board
BMB Report
Journal Ad-hoc Reviewer
Science Translational Medicine
Cancer Research
Molecular Cancer Research
International Journal of Cancer
EBioMedicine
FEBS Letters
Scientific Reports
BMC Cancer
PLOS One
Molecular and Cellular Endocinology
Oncology Reports
Biochemistry and Cell Biology
Grant Ad-hoc Reviewer
The Academy of Medical Sciences Newton Advanced Fellowship, UK
French National Cancer Institute (INCa), France
Alan B. Slifka Foundation
Alaska INBRE Pilot Research Project
Breast Cancer Now, UK
State of Florida Department of Health

Affiliations

American Association for Cancer Research (AACR)
Active Member (2002 - present)
American Thoracic Society (ATS)
Full Member (2017 - present)

Funding

5P50CA70907 (PI: Minna, Career Enhancement Program PI: Kim)
- NIH/NCI Lung Cancer SPORE (UTSW/MD Anderson) [2016/09–2018/12]
Distinct Glycolytic Phenotypes of Lung Squamous Cell Carcinoma Dictate Selective Vulnerability to HIF-1/GLUT1 Inhibition
RP160617 (PI: Zhang, Co-Investigator: Kim)
- Cancer Prevention and Research Institute of Texas (CPRIT) Individual Investigator Award [2016/03–2019/02]
Optimizing Therapeutic Strategies against Lung Cancer using Multi-Modality Imaging
PFF-310063 (PI, Kim)
- Pulmonary Fibrosis Foundation I M Rosenzweig Young Investigator Award [2014/07–2016/06]
Evaluation of Hypoxia-inducible Factor-1 Signaling as Anti-Fibrotic Therapy