Verline Justilien, Ph.D.

Location

Contact

SUMMARY

Verline Justilien, Ph.D., is interested in the genetics, biochemistry and cell biology of lung cancer. She is particularly interested in identifying the genetic and epigenetic alterations and their associated molecular signaling mechanisms that occur in lung cancer cells of origin and drive tumor initiation, progression, maintenance, metastasis and chemoresistance. She aims to translate this knowledge into better therapeutic strategies for lung cancer.

Dr. Justilien's studies use a combination of cell-based in vitro and in vivo tumor models, molecular and cell biology, genomic, proteomic, and bioinformatics approaches.

Focus areas

• Novel nuclear epithelial cell transforming sequence 2 (Ect2) functions in cellular transformation. There is a long-recognized association between ribosome biogenesis and cellular transformation. Cancer cells produce elevated levels of rRNA and ribosomes to sustain their rapid uncontrolled growth. However, the mechanistic links between rRNA synthesis and cancer are not well-understood. Dr. Justilien's research has identified Ect2, a guanine nucleotide exchange factor that activates Rho family GTPases in cellular signaling, as an oncoprotein in lung cancer. Dr. Justilien's studies have shown that Ect2 activates rRNA synthesis to promote the transformed behavior of lung cancer cells. Dr. Justilien is interested in determining the mechanisms by which Ect2 engages the rDNA transcriptional machinery to enhance rRNA synthesis in lung cancer cells.

  In addition to studying rDNA synthesis, Dr. Justilien is interested in determining whether Ect2 may act as a direct transcriptional regulator of other genes to promote lung cell transformation. Dr. Justilien's studies demonstrate that lung cancer cells exhibiting elevated Ect2-mediated rDNA transcription are highly sensitive to the growth inhibitory effects of selective polymerase I inhibitors, which target rDNA transcription. Dr. Justilien is interested in developing combined therapies with polymerase I inhibitors as a treatment approach for lung and other Ect2-dependent human cancers.

• Lung squamous cell carcinoma (LSCC) initiation and pathological progression. A major subtype accounting for 30 percent of lung cancer diagnoses, LSCC is characterized by poor therapeutic response, a high relapse rate, poor prognosis and a lack of actionable oncogene targets. Furthermore, the molecular events that drive LSCC initiation and progression remain incompletely understood. Global genomic analyses of people with primary human LSCC demonstrate that among the most prevalent recurrent genetic alterations in LSCC are copy number gains (CNGs) in chromosome 3q26, which occur in approximately 80 percent of LSCCs.

  Dr. Justilien's work has demonstrated that at least three 3q26 genes (PKCζ Ect2 and Sox2) functionally collaborate in LSCC transformation. Dr. Justilien is interested in determining how these oncoproteins collaborate in LSCC tumor initiation, progression, maintenance, metastasis and chemoresistance and translating that knowledge into better therapeutic strategies for LSCC. CNGs in 3q26 are also prevalent in bladder, breast, cervical, esophageal, head and neck, kidney, serous ovarian, stomach, and uterine cancers. Therefore, results from her studies in LSCC may also provide insight into the biology and therapeutic targeting of these other human cancer types.

Significance to patient care

Dr. Justilien's goal is to enhance the understanding of lung cancer in a clinically meaningful way. She aims to identify oncogenic drivers of lung tumorigenesis and their associated oncogenic signaling pathways to improve understanding of lung cancer initiation and pathological progression. This knowledge will allow for the identification of markers for early lung cancer detection and diagnosis and will facilitate the design of innovative strategies for lung cancer treatment.

Professional highlights

• Recipient, Minority Scholar in Cancer Research Award, American Association for Cancer Research, 2014
• Recipient, Young Investigator Award, Biochemical Journal, 2009