Kathleen Conklin, Ph.D.

Associate Professor
Dept. of Genetics, Cell Biology and Development
Office: 4-150A MT
Phone: (612) 626-0445
Fax: (612) 626-0731
e-mail: kathleen@mail.med.umn.edu website

RESEARCH INTERESTS

Oncogenesis, retroviruses, arboviruses

There are three major projects in the laboratory. The first involves the identification of genes involved in development of human leukemia. This project is a collaborative effort between my laboratory and that of Dr. Betsy Hirsh. Dr Hirsch's laboratory has identified a new recurrent chromosomal abnormality in young children with acute myeloid leukemia. We are cloning genes that localize to the sites of chromosomal rearrangements in tumors from these patients; one candidate gene we identified recently is novel and exhibits characteristics of a tumor suppressor gene. Studies are underway to define the function in both normal and leukemic cells of this and additional genes being cloned.

The second project takes a different approach to identify genes important in tumorigenesis and uses a retrovirus model. Many retroviruses induce leukemias; analysis of tumor DNA demonstrates that viral DNA (called a provirus) is found inserted at common sites and that these sites frequently define either oncogenes or tumor suppressor genes. We are analyzing both myeloid and B cell tumors induced by different strains of retroviruses to identify genes that are aberrantly regulated after proviral insertion. As an extension of these tumorigenesis studies, we are also investigating the role of several viral genes required for efficient replication.

The third project is new and focuses on developing Drosophila as an experimental host for arboviruses. Our goal is to be able to use the power of Drosophila genetics to identify host proteins required for replication of this important group of viruses in non-vertebrate hosts. Arboviruses are a large group of viruses that are spread by arthropods (arthropod-borne viruses). We are interested in those that are transmitted by mosquitoes and that induce encephalitis in infected vertebrates; examples include Sindbis virus, West Nile Virus, La Crosse Virus, and Equine encephalitis virus. This project is being conducted in collaboration with Dr. Tom Hays, a Drosophila geneticist and expert in molecular motors. Our initial studies demonstrate that Sindbis replicates efficiently in Drosophila, establishing the potential utility of this approach. The two main areas we plan to investigate are (1) to determine why arbovirus infection of most vertebrate cells leads to apoptotic cell death while insect cells are relatively unaffected by virus infection and (2) to define the molecular motors responsible for intracellular virus transport.

Website: http://www.gcd.med.umn.edu/faculty/conklin.html

Recent Publications

• Houtz, E. and K.F. Conklin. 1996. Identification of EFIV, a stable factor present in many avian cell types that transactivates sequences in the 5' portion of the Rous Sarcoma Virus Long Terminal Repeat Enhancer. J. Virol. 70:393-401.
• Benson, S.J., B.L. Ruis, A.L. Garbers, A.M. Fadly and K.F. Conklin. 1998. Independent isolates of the emerging subgroup J avian leukosis virus derive from a common ancestor. J. Virol. 72: 10301-10304.
• Benson, S.J., B.L. Ruis, A.M. Fadly and K. F. Conklin. 1998. The unique envelope gene of the subgroup J avian leukosis virus derives from ev/J proviruses, a novel family of avian endogenous viruses. J. Virol. 72:10157-10164.
• Ruis, B.L., S.J. Benson, and K.F Conklin. 1999. Genome structure and expression of the ev/J family of avian endogenous viruses. J. Virol. 73:5345-5355.