OHSU Knight Cancer Institute

Kim Lab

Understanding cancer development and progression

Welcome to the Kim Lab! We are working to understand a reversible regulatory mechanism underlying cancer development and progression and aim to apply our findings in early cancer therapy.

Jungsun Kim, Ph.D., is an assistant professor of Molecular and Medical Genetics in the OHSU School of Medicine and member of the OHSU Knight Cancer Institute's Cancer Early Detection Advanced Research (CEDAR) Center

The lab is based in the Knight Cancer Research Building, a state-of-the-art research facility designed to support a collaborative atmosphere that brings multidisciplinary scientists together under one roof. The lab is also affiliated with the Graduate Program in Biomedical Sciences (PBMS) at OHSU.

About our research

In normal development, the cell fate is well-orchestrated through multiple layers of gene regulation by chromatin states and master transcription factors; failed regulation in this context often leads to tumorigenesis. Our group strives to understand the molecular basis of epigenetic rewiring of cell fates, which are essential to a number of processes, including embryonic development, cancer development, and cellular reprogramming.

To study this complex process, we integrate multidisciplinary approaches such as cellular reprogramming, cancer biology, stem cell biology, genomics, bioinformatics, in vivo reporter system, and imaging. We eventually hope to harness this information to offer an epigenetic-based target for cancer treatment. 

Kim Lab members
Lab members Taelor Ekstrom, Christopher Markgraf, Junsung Kim and Dmytro Grygoryev, 2021.

Projects

Our research focuses on reprogramming and programming of cancer. Learn more below.

Cell fate, or identity, is well-maintained through multiple chromatin states established by master transcription factors (TFs) and chromatin regulators. Dysregulation of the determination of cell identity may lead to tumorigenesis, and indeed dysregulated master TFs in cancer cells can dictate a cancer cell’s epigenetic landscape and cell state. 

A defined set of TFs can reprogram somatic cells into induced pluripotent stem cells (iPSCs) by rewiring the reversible epigenetic landscape of “starting” somatic cells, which is established by cell fate decisions during normal development. This led to the intriguing possibility that TF-mediated reprogramming may offer a tool to rewire and reverse aberrant epigenetic alterations in cancer cells.

Indeed, we demonstrated a proof-principle of a pancreatic cancer reprogramming model that provides a human cell model for unprecedented experimental access to different stages of human pancreatic cancer. Using this system, we uncovered a regulatory network and a secreted or released protein that can discriminate early resectable stage I pancreatic cancer patients as well as all stages of PDAC from healthy controls (Kim et al., 2013 Cell Reports; Kim et al., 2017 Science Translational Medicine).  

We are interested in addressing the following questions:; i) to what extent and how reproducibly aberrant cancer transcriptional networks can be destabilized through TF-mediated reprogramming, ii) how cells that fail reprogramming regain an aggressive tumor phenotype, and iii) what chromatin regulators maintain a cancer cell state. Addressing these questions will provide novel insight into how cancer cells establish and maintain cancer identity.

The death rate of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) has risen since 1990, and PDAC is expected to be the second leading cause of cancer death by 2020-25. Detecting PDAC at early stages when surgery and treatment can be effective is the best hope to improve the disease's dismal prognosis. 

A detailed understanding of the progression from PanIN to PDAC could facilitate the development of early detection strategies and therapies that reduce the malignancy. A growing body of evidence indicates that PDAC can be disseminated very early in humans and mice. However, remarkably, little is known about early dissemination, mainly due to a lack of human models to study disease progression.

Utilizing our cancer model system and newly developed reporter systems that allow tracking cancer cells in vivo, we aim to reveal key mechanistic effectors during human PDAC progression. We also aim to characterize a subset of disseminating cells in early PDAC progression that clinically impacts the prognosis.

Meet our team

Principal investigator

CEDAR members

  • Christopher Markgraf, B.S., summer intern, 2021
  • Breeshey Roskams-Hieter, B.S., CEDAR bioinformatic scientist, 2018-2021, currently a graduate student at the University of Edinburgh
  • Shannon Babcock, PMCB rotation student, 2020
  • Junha Lee, high school intern, 2019-2020
  • Jairie Jimenez, CEDAR research assistant II, 2019
  • Mona Mohammadhosseini, PMCB rotation student, 2019
  • Setareh Sharzehi, PMCB rotation student, 2019
  • Julien Tessier, CEDAR research associate, 2018-2019, currently at biopharmaceutical company Sanofi
  • Dallas Garreaud, Summer Equity Research Intern, 2018

Let's connect!

Members of the Kim Lab

Are you a highly motivated and talented postdoctoral fellow? 

Email a brief description of your research interests and your CV to get the conversation started. PBMS students are also welcome.

Publications

Check out some of our featured work below. You can also view a complete list of our publications on PubMed and our Open Researcher and Contributor ID (ORCID) profile.

Kim J. Cellular reprogramming to model and study epigenetic alterations in cancer. Stem Cell Research 2020, 49, 102062 [Review]

Kim J, Bamlet WR, Oberg AL, Chaffee KG, Donahue G, Cao XJ, Chari S, Garcia BA, Petersen GM, Zaret KS. Combined THBS2 and CA19-9 blood based markers detect early pancreatic ductal adenocarcinoma. Science Translational Medicine 2017 Jul 12;9 (398)

Kim J and Zaret KS. Reprogramming of human cancer cells to pluripotency for models of cancer progression. The EMBO Journal 2015, 34: 739–747 [Review]

Kim J, Hoffman JP, Alpaugh RK, Rhim AD, Reichert M, Stanger BZ, Furth EE, Sepulveda AR, Yuan CX, Won KJ, Donahue G, Sands J, Gumbs A, and Zaret KS. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Reports 2013, 3: 2088–2099

Kim J*, Donahue G, Yang W, and Zaret KS. Longitudinal analysis of pancreatic adenocarcinoma development reveals transient gene signatures (in press, Molecular Cancer Research, *Corresponding author)

"Cellular reprogramming provides a potential new model to study disease progression in cancer", Science Featured Series, 2021 July 19

Protein biomarker for pancreatic ductal adenocarcinoma” by Talha Burki, Research Highlight, Lancet Oncology, 2017 Jul 20

Biomarkers for the early detection of PDAC” by Ray K, Research Highlight. Nat Rev Gastroenterol Hepatol. 2017 doi: 10.1038/nrgastro.2017.111.

"New Biomarker Identified for PDAC", News in Brief, Cancer Discovery, 2017, DOI: 10.1158/2159-8290.CD-NB2017-107

"A Dish of Pancreas" by Gilbert Chin and Maria Cruz, Editor’s Choice, Science, 2013 July 26.

"Learning about Cancer by Studying Stem Cells" by Sharon Reynolds, Research Highlight, NIGMS Inside Life Science, 2014 Jan 8.

2017 Science Translational Medicine paper was selected as one of the Most Life-Changing Medical Breakthroughs of 2017 in Prevention magazine, 2017 Dec issue; The New Times magazine, 2017 Dec 25

Blood test holds promise for earlier pancreatic cancer detection” 2017 Science Translational Medicine paper was featured in the CBS News, U.S.News & World Report, MSN Canada, The Japan Times, New China News, La Razón, Correio Braziliense News, Science Daily, NCI Cancer Current, and so on.

Blood test for early detection of pancreatic cancer headed to clinic” 2017 Science Translational Medicine paper was featured in the Penn Medicine News. 2017 July 12

Pluripotent Stem Cells Made From Pancreatic Cancer Cells Are First Human Model of the Cancer's Progression”, 2013 Cell Reports paper was featured in Penn Medicine News, June 20, 2013, and ESC & iPSC NEWS vol 8.25, 2013 Jun 26

"Pluripotent cells from pancreatic cancer cells first human model of cancer's progression", 2013 Cell Reports paper was featured in EurekAlert, AAAS, 2013 June 20

We love what we do

We're passionate about our research and have fun inside and outside the lab. 

Members of the Kim Lab

Working in the lab at the Knight Cancer Research Building. 

Kim Lab experiment

Here's one of our first experiments.

Kim Lab activities

We got together for a round of parking lot mini golf.