Novel Biomarker that Discriminates Indolent from

Aggressive Phenotype in AA Men

NIH U54MD008620

M. Saleem Bhat, PhDAsst. ProfessorHormel Institute,

University of Minnesota

Prostate cancer (CaP) exhibits the most striking racial disparity. African-Americans are at 1.4 times higher risk of

being diagnosed of CaP than Caucasians.

Serum-PSA as a disease type discriminating marker is reported to perform poor in African-American men.

There is no race-specific biomarker that would provide information at the time of diagnosis if the

tumor is treatable or has tendency to spread to other parts of body (metastasis) and become resistant to

therapies.

Hypothesis: ROBO1 could act as a potential biomarker that would

discriminate between primary and metastatic disease in African-Americans, and possibly a therapeutic target to

treat metastatic CaP in this population.

Laboratory Research Plan:Aim#1: Determine the relevance of ROBO1 as a biomarker for CaP-

disease phenotype-distinction and aggressiveness in African-Americans using IHC analysis of tissues.

Aim#2: Determine if hypermethylation of ROBO1 would predict the localized or metastatic phenotype of prostate cancer.

Aim# 3: Investigate the relevance of ROBO1 as a therapeutic target using race-distinct carcinogenesis model.

To address issue of disparity, we will employ :1. Laboratory based research

2. Involvement of minority community in understanding the gravity of the this health problem,

Academic-Community Partnership & Plan:The PI will impart the health disparity research training to an

African-American student (identified by The 100 Black Men Inc. through its education/fellowship program)

Aim#1: Determine the relevance of ROBO1 as a biomarker for CaP-disease using IHC analysis of tissues. Update

We obtained >60 AA-patient Specimens. We perfected the method; Performed validation of several antibodies against ROBO1

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Status : Going on

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Aim#2: Determine if hypermethylation of ROBO1 would predict the localized or metastatic phenotype of prostate cancer.

Update

Plan: We would use prostatic tissues and circulatory DNA (proof of the principle) in serum samples of African-American patients.

We are isolating the DNA from available prostatic tissues. We also plan to use LCM dissection technique for isolating ROBO1+ve and ROBO1-ve area of tissues to isolate DNA and perform methylation analysis .We would perform the methylation analysis of all DNA samplesunder similar condition.We standardized of isolating free DNA from serum samples.

Aim# 3: Investigate the relevance of ROBO1 as a therapeutic target using race-distinct carcinogenesis model.

Using race-distinct in vitro models we will determine if reactivating ROBO is an ideal therapeutic strategy for treating metastatic-CaP disease in African-Americans

Update

2. We are currently generating AA-specific localized and metastatic cell lines in which the expression of ROBO1 can be switched on and off as per need.

3. We have started experiments to study the molecular pathways which could be involved in the regulation of the differential expression of ROBO1 in the localized and metastatic tumor stages of CaP disease.

1.We have generated cell lines Representing docetaxel-resistant and bicalutamide-resistant disease in African-American men.

NIH U54MD008620

Academic-Community Partnership

1. (With the help of Dr. Mark Alexander ), The 100 Black Men , the community partner of CHAAMPS program has identified and nominated one student for a 10-week long training in Health

Disparity research in my laboratory. We anticipate that the student start the training in the mid-April, 2016.

Update

Funding : NIH/NIMHDAcknowledgment

Collaborators:1. Dr. Koochekpour (Roswell Cancer Institute, Buffalo, NY).

2. Louisiana-North Carolina Prostate Cancer Consortium

3. Dr. Mark Alexander , 100 Black Men of America, Inc.

4. Dr. Badrinath Konety, Department of Urology, University of Minnesota

NIH U54MD008620