Randal K. Wada, M.D.

Site Map
General Information
Center Directory
News and Events
Grants and Publications
Employment
E-mail access for CRCH Staff only
Cancer Research Center of Hawaii

Randal K. Wada, M.D.
Associate Professor (Researcher), Cancer Research Center of Hawaii;
Associate Professor of Genetics and Molecular Biology, John A. Burns School of Medicine;
Graduate Faculty, Cell, Molecular, and Neuroscience Program, College of Natural Sciences;
Associate Professor of Pediatrics, John A. Burns School of Medicine
M.S. (Biological Sciences), Northwestern University;
M.D., Emory University;
American Board of Pediatrics, American Board of Pediatrics Sub-Board Hematology/Oncology
tbear@crch.hawaii.edu

Publication list via PubMed

Regulation of N-myc Oncogene in Human Neuroblastoma

Neuroblastoma is a common childhood tumor that is usually not diagnosed until it has become widespread. Survival rates in children with advanced neuroblastoma have not enjoyed the large gains seen in other forms of pediatric cancer. Recently however, results of a national clinical trial showed that the addition of retinoic acid (RA) after conventional therapy significantly improved disease free survival.

This naturally occurring dietary compound causes neuroblastoma cells growing in culture to mature and differentiate into benign nerve cells. It is felt that this is what happens in patients treated with RA. A key event in the ability of RA to induce maturation in these cells is its effect on the MYCN gene, which plays a major role in the biology of neuroblastoma. Shutting off MYCN is the first step in getting neuroblastoma cells to stop dividing and begin the maturation process. Loss of the ability to turn down MYCN production is associated with a failure of tumor cells to differentiate in response to RA treatment.

Despite its importance in understanding how differentiation therapy might work, nothing is known about the molecular switch that turns the MYCN gene off after tumor cells get exposed to RA. Traditional methods of gene analysis have not been able to address this question because they only focus on a small region of DNA at a time. Work in this lab uses new analytical techniques that allow the simultaneous examination of multiple sites along the MYCN gene’s control region, as well as the detection of regions on other chromosomes that might interact with the MYCN control region. It is hoped that this approach will identify DNA regions that interact in a cooperative fashion to shut the gene off, and that knowledge of these DNA sequences will lead to the identification of the regulatory proteins that bind to them. Such information will ultimately enable the development of molecular tests to determine which patients have tumors that might be resistant to RA, and may provide leads as to alternative therapeutic approaches. These patients could then be triaged to receive other drugs instead of or in addition to RA that would increase their chances of staying in remission.

Selected Publications
Wada RK, Bradford A, Kanemaru KK, Tutthill MC, Takeuchi KK, Sidell N, Wada RK. Retinoic acid induced downregulation of MYCN is not mediated through changes in Sp1/Sp3. Pediatr Blood Cancer, in press.

Wada RK, Bradford A, Yim R, Drachman J, Strong MD, Rheems JA. Cord blood units collected at a remote site: A collaborative endeavor to collect umbilical cord blood through the Hawaii Cord Blood Bank and store units at the Puget Sound Blood Center. Transfusion 44:111-8, 2004.

Tuthill MC, Wada RK, Arimoto JM, Sugino CN, Kanemaru KK, Takeuchi KK, Sidell N. N-myc oncogene expression in neuroblastoma is driven by Sp1 and Sp3. Mol Genet Metab 80:272-80, 2003.

Sidell N, Pasquali M, Malkapuram S, Wanichkul T, Wada RK. In vitro and in vivo effects of easily administered, low toxic retinoid and phenylacetate compounds on human neu-roblastoma cells. Br J Cancer 89:412-9, 2003.

Han SW, Wada RK, Sidell N. Differentiation of human neuroblastoma by phenylacetate is mediated by peroxisome proliferator-activated receptor gamma (PPARg ). Cancer Res 61:3998-4002, 2001.

Back to Center Member Lists