Associate Professor

Postdoc: Dana-Farber Cancer Institute, Harvard Medical School

Ph.D.: Washington University in St. Louis

B.S.: Seoul National University, South Korea

DNA replication and repair pathways in cancer therapy

Genome instability and cancer


Our laboratory wishes to elucidate fundamental mechanisms of DNA repair with a goal of developing anti-cancer targets and biomarkers for therapeutic benefits. Genome instability, a high frequency of DNA mutations primarily caused by defective DNA repair, is one of the most pervasive characteristics of cancer, contributing to the pathogenesis of both hereditary and sporadic cancers. The DNA repair system constitutes a critical tumor suppressor network to preserve genomic integrity, thereby preventing the onset and progression of tumor. Therapeutic interventions that exploit deregulated DNA repair in cancer allow us to induce synthetic lethality (as highlighted by a recent FDA approval of a PARP inhibitor to treat advanced ovarian cancer with defective BRCA1/2 genes) or augment the efficacy of cytotoxic chemotherapy. Thus, knowledge on the regulatory schemes of DNA repair will not only provide insights into cancer etiology in light of genome instability but also facilitate the development of novel cancer therapeutics. Using cellular, biochemical, and genetic approaches, we are investigating DNA repair mechanisms associated with DNA replication, focusing on explicating the role of proteolysis in regulating these steps.

The Fanconi anemia (FA) pathway

The FA pathway resolves stalled replication forks in response to DNA interstrand cross-links (ICLs), lethal lesions that block DNA replication and transcription. Currently, 22 FA gene products constitute the FA pathway, and germ-line mutations in this pathway lead to bone marrow failure and cancer predisposition. Central to the FA pathway is monoubiquitination of the FANCD2 protein by the FA core ubiquitin E3 ligase complex, which in turn recruits enzymes necessary for processing ICLs. Thus, the activity of the FA core complex needs to be tightly controlled to recognize lesions and initiate repair. Indeed, in addition to its catalytic core, the FA core complex is composed of multiple subunits that can be potentially regulated by a variety of posttranslational modifications. We are focusing on the proteolytic mechanisms that control the activity of the FA core complex, which would dictate the outcome of DNA ICL repair and chemotherapeutic response, and investigating the impact of their deregulation to tumorigenesis.

DNA replication stress response

Due to their hyper-proliferative nature, cancer cells are often selected for the loss of mechanisms to control DNA replication, thereby exhibiting elevated levels of replication problems. Replication stress, defined as the perturbation of DNA replication by endogenous and exogenous obstacles ranging from a structural hindrance to fork progression to a shortage of replication factors, is therefore a key source of genome instability and tumorigenesis. However, this also provides a therapeutic opportunity where we can exacerbate the replication stress of cancer cells to achieve specific killing of cancer cells, as exemplified by a recent development of checkpoint inhibitors for cancer therapy. Proliferating cell nuclear antigen (PCNA) is a processivity factor that guides DNA polymerases at replication forks and plays a critical role in coordinating DNA replication and responses to replication stress. We are focusing on identifying the mechanisms by which various genome surveillance factors preserve the integrity of replication forks in association with the PCNA interaction and ubiquitin signaling, which would provide a therapeutic opportunity to exploit the vulnerability of cancer cells with replication problems.

A complete list of publications can be found in HERE.

Hyungjin Kim, Ph.D. 

Associate Professor

Department of Pharmacological Sciences

Renaissance School of Medicine and the Cancer Center

Basic Sciences Tower 8-125

Stony Brook University


Office: 631-444-3134