Dr Arul Chinnaiyan

Dr. Arul Chinnaiyan is the S.P. Hicks Endowed Professor of Pathology, Director of the Michigan Center for Translational Pathology (MCTP) and a Howard Hughes Medical Institute Investigator in patient-oriented research and an American Cancer Society Research Professor.  He was elected to the National Academy of Medicine in 2009. He has received a number of prestigious awards including the Pew Biomedical Scholar Award, the Amgen Outstanding Investigator Award, AACR Outstanding Investigator Award, the Benjamin Castleman Award, Paul Marks Prize for Cancer Research. Most notably, his research group was the recipient of the 2007 AACR Team Science award for the discovery of recurrent gene fusions in prostate cancer. He was also elected Member of the American Academy of Arts & Sciences and was named 2014 National Academy of Inventors Fellows. He also led the development of the popular cancer profiling bioinformatics resource called Oncomine (www.oncomine.org) (hosting over 20,000 registered users from over 30 countries and serving 16 of the 20 top oncology biopharma). 

 

Dr. Chinnaiyan’s lab is focused on functional genomic, proteomic and bioinformatics approaches to study cancer for the purposes of understanding cancer biology as well as to discover clinical biomarkers.  Over the past few years, the Chinnaiyan Lab has been involved in developing high-throughput clinical sequencing approaches for precision oncology.  In April of 2011, the Michigan Oncology Sequencing Center (MI-ONCOSEQ) clinical sequencing study was established and a pilot “proof-of-principle” study was conducted which prospectively enrolled patients with advanced cancers for comprehensive mutational analysis (Sci Trans Med, 3: 111ra121). An “integrative sequencing approach”, whole exome and transcriptome sequencing carried out in a CLIA-certified laboratory, is utilized to provide a comprehensive landscape of the genetic alterations in individual tumor specimens for the purpose of identifying informative and/or actionable mutations. This approach enables the detection of point mutations, insertions/deletions, gene fusions and rearrangements, amplifications/deletions, and outlier expressed genes. Furthermore, we can identify certain germline alterations that may also be relevant. Thus far over 1000 adult and pediatric (through PEDS-ONCOSEQ) patients have undergone clinical sequence analysis, for many of whom actionable mutations were identified and suggested therapies that would otherwise not be considered. He has recently applied these clinical sequencing approaches to the pediatric oncology population (JAMA, Sept. 2015).

 

MI-ONCOSEQ has led to a number of important discoveries including the pathognomomic gene fusion for solitary fibrous tumor (SFT) as well as diverse targetable gene fusions of FGFR across a diverse array of common solid tumors. We also identified activating mutations in ESR1 that are a key mechanism in acquired endocrine resistance in breast cancer therapy. In collaboration with the Prostate Cancer Foundation-Stand Up 2 Cancer (PCF-SU2C) International Dream Team Consortium, the Chinnaiyan group led the study to develop a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC) by obtaining a comprehensive landscape of cancer-related mutations in order to potentially incorporate this information for therapeutic strategies and/or enrolling subjects into appropriate clinical trials (Cell May 2015). This study showed that approximately a quarter of patients harbor defects in the DNA repair pathway which make them susceptible to PARP inhibitors.  He collaborated with Dr. Johann de Bono to show that metastatic prostate cancer patients with DNA repair defects respond preferentially to the PARP inhibitor olaparib (NEJM Oct 2015). This work led to the FDA breakthrough designation and approval of olaparib for the treatment of metastatic prostate cancer with defects in DNA repair in January of 2016.

 

Dr.  Chinnaiyan was part of a delegation from that American Association of Cancer Research (AACR) that met with Vice President Biden’s staff in January of 2016 to discuss opportunities in precision medicine for the treatment of cancer. These discussions, along with others, provided input into President Obama’s proposed $1 Billion Cancer “Moonshot” to cure cancer announced in February.   


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