Kathleen Kelly, Ph.D.

Kathleen Kelly, Ph.D.
Chief
Senior Investigator
Head, Signal Transduction Section
CCR Deputy Director

Dr. Kelly’s program investigates mechanisms of prostate cancer tumorigenesis and progression. A major area of focus addresses the roles of oncogenotype, tumor heterogeneity/cancer stem cells, and metabolism in the development of therapeutic responses, especially for castrate resistant prostate cancer. Additional research investigates signal transduction pathways that influence prostate cancer bone metastasis. As chief of LGCP, Dr. Kelly advances integration with the clinical prostate cancer program to carry out mechanism-based translational studies using a variety of pathological, genomic, and patient-derived live culture approaches.

Areas of Expertise
1) Prostate cancer 2) Organoid cultures 3) Drug response and resistance 4) Metabolism and imaging 5) Cancer stem cells 6) Oncogenomes

Contact Info

Kathleen Kelly, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 1068
Bethesda, MD 20892
Ph: 240-760-6827
kellyka@mail.nih.gov

Research Interests

Our laboratory focuses on understanding the mechanistic consequences of specific genetic alterations that lead to the development of prostate cancer (PC), especially as related to progression. Prostate cancer (PC) is the most frequently diagnosed non-cutaneous cancer in men, and although organ confined PC is highly treatable with surgery and/or radiation, metastatic disease is incurable and leads to significant morbidity and mortality. Our goal is to improve detection and treatment of prostate cancer through understanding genomic and biochemical mechanisms of disease progression.

We use two complementary approaches, patient-derived xenografts/organoids and genetically engineered mouse models (GEMMs). A strength of our laboratory is our ability to employ a wide variety of in vivo models and imaging modalities. We use the large cohort of LuCaP patient-derived CRPC xenografts established by our collaborators at the University of Washington. The LuCaP cohort represents the genotypic and phenotypic heterogeneity of advanced prostate cancer clinical samples. To facilitate experimental manipulations, including genetic modifications and high throughput screening assays, we optimized organoid methods for establishing and maintaining in vitro cultures of LuCaP xenograft tumor cells. In addition to the LuCaP organoids, we also have developed a number of organoid cultures from NIH clinical center CRPC patient biopsy samples. Together these organoid cultures in combination with matching PDX tumors provide an extensive, clinically-relevant experimental platform. One major effort is focused upon high throughput screens to determine therapeutic sensitivity and metabolic characteristics (including imaging tools) as they relate to molecular characteristics. A second effort addresses the genetic and epigenetic mechanisms of CRPC dedifferentiation and neuroendocrine transdifferentiation that occurs in response to androgen deprivation.

GEMMs are particularly useful for the availability of genetically-defined tumor tissue, the ability to longitudinally investigate various stages of prostate cancer progression, and the ease of manipulating the hormone environment. Models of aggressive CRPC in mice have provided insight into poorly differentiated tumors enriched for cancer stem/progenitor cells. Combined PTEN/TP53 mutations occur in ~30% of clinical CRPC. Our characterization of a Pten/Tp53 null prostate cancer GEMM model revealed that the amplification and plasticity of luminal prostate cancer progenitor cells contributes to the aggressive and castration resistant nature of the disease. Ongoing investigations are focused upon the signaling pathways that promote self-renewing cancer stem cells and their relationship to castration indifference.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Genetics and Genomics
View Dr. Kelly's PubMed Summary.

Selected Recent Publications

  1. Beshiri ML, Tice CM, Tran C, Nguyen HM, Sowalsky AG, Agarwal S, Jansson KH, Yang Q, McGowen KM, Yin JJ, Alilin AN, Karzai FH, Dahut WL, Corey E, Kelly K.
    Clinical Cancer Research. In Press: 2018. [ Journal Article ]
  2. Ward Y, Lake R, Faraji F, Sperger J, Martin P, Gilliard C, Ku KP, Rodems T, Niles D, Tillman H, Yin J, Hunter K, Sowalsky AG, Lang J, Kelly K.
    Cell Reports. 23(3): 808-822, 2018. [ Journal Article ]
  3. Martin PL, Yin JJ, Seng V, Casey O, Corey E, Morrissey C, Simpson RM, Kelly K.
    Oncogene. 36(4): 525-533, 2017. [ Journal Article ]
  4. Agarwal S, Hynes PG, Tillman HS, Lake R, Abou-Kheir WG, Fang L, Casey OM, Ameri AH, Martin PL, Yin JJ, Iaquinta PJ, Karthaus WR, Clevers HC, Sawyers CL, Kelly K.
    Cell Reports. 13(10): 2147-2158, 2015. [ Journal Article ]
  5. Liu YN, Abou-Kheir W, Yin JJ, Fang L, Hynes P, Casey O, Hu D, Wan Y, Seng V, Sheppard-Tillman H, Martin P, Kelly K.
    Mol. Cell. Biol. 32: 941-53, 2012. [ Journal Article ]

Dr. Kelly received her Ph.D. from the University of California, Irvine. She completed her postdoctoral training in the laboratory of Philip Leder, Harvard Medical School, and she has maintained an independent research program at the NCI since 1984. Dr. Kelly's interests have focused on the genetic regulation of cell growth, cancer progression and metastasis.

Name Position
Supreet Agarwal, Ph.D. Postdoctoral Fellow (Visiting)
Aian Neil Alilin Animal Technician (Contr.)
Michael L. Beshiri, Ph.D. Postdoctoral Fellow (CRTA)
Keith H. Jansson, Ph.D. Postdoctoral Fellow (CRTA)
Julianna Kostas B.S. Postbaccalaureate Fellow (CRTA)
Lechen (Frank) Li Ph.D. Special Volunteer
Morgan Riba B.S. Postbaccalaureate Fellow (CRTA)
Hoa Tieu MRI Technician (Contr)
Margaret White Ph.D. Postdoctoral Fellow (CRTA)
Ivy Yin, Ph.D. Research Biologist