Nima Sharifi, M.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:NB4-79
sharifn@ccf.org
Phone: (216) 445-9750
Fax: (216) 445-6269



Our laboratory is focused on steroid metabolism and androgen receptor (AR) function as it relates to prostate cancer. The first line of therapy for metastatic prostate cancer is androgen deprivation therapy (ADT), which blocks the release of gonadal testosterone and suppresses intratumoral concentrations of the most potent androgen, dihydrotestosterone (DHT). However, metastatic disease eventually becomes resistant to ADT. Prostate cancer that progresses in the face of ADT is termed castration-resistant prostate cancer (CRPC) and is frequently driven by tumors acquiring the capability of making their own DHT. We study how this process occurs. Our most important discoveries include identification of the first mutation in the androgen synthesis machinery that is responsible for increasing DHT synthesis in CRPC, demonstration that DHT synthesis in patients with CRPC follows a pathway that circumvents testosterone, and the identification of abiraterone metabolites that impinge upon the androgen axis and regulate treatment response. We are currently applying these findings to the study of CRPC as it occurs in patients.

In other words ...

I am a medical oncologist and physician-scientist with a sole clinical and scientific focus on prostate cancer. Androgens are a driving force in prostate cancer disease progression.  As such, for seven decades the upfront treatment of advanced prostate cancer has been depriving tumors of this driving force (androgens).  Unfortunately, treatment resistance almost always occurs in metastatic prostate cancer, through tumors making their own androgens.  We study how these tumors make their own androgens with a view toward blocking these pathways with the development of new treatment modalities.  Our hope is that these discoveries will eventually be brought to the clinic for the benefit of men with prostate cancer.  We work closely with our colleagues at Cleveland Clinic and other collaborators from around the world to make this happen. 


Mohammad  Alyamani
Mohammad Alyamani
Graduate Student

Location:NB4-79
Phone:(216) 445-9751
alyamam@ccf.org
Fax:(216) 445-6269
laboratory

Mehdi  Baratchian Ph.D.
Mehdi Baratchian Ph.D.
Postdoctoral Fellow

Location:NB4-25
Phone:(216) 445-9752
baratcm@ccf.org
Fax:(216) 445-6269
laboratory

Michael P. Berk M.S.
Michael P. Berk M.S.
Lead Research Technologist

Location:NB4-90
Phone:(216) 445-9752
berkm@ccf.org
Fax:(216) 445-6269
laboratory

Kelsey  Bohn Ph.D.
Kelsey Bohn Ph.D.
Postdoctoral Fellow

Location:NB4-15
Phone:(216) 445-9752
bohnk@ccf.org
Fax:(216) 445-6269
laboratory

Yoon-Mi  Chung M.S.
Yoon-Mi Chung M.S.
Lead Research Technologist

Location:NB4-137
Phone:(216) 445-9751
chungy2@ccf.org
Fax:(216) 445-6269
laboratory

Charlie  Dai B.S.
Charlie Dai B.S.
HHMI Medical Student

Location:NB4-15
Phone:(216) 445-9752
daic@ccf.org
Fax:(216) 445-6269
laboratory

Aimalie  Hardaway Ph.D.
Aimalie Hardaway Ph.D.
Postdoctoral Fellow

Location:NB4-15
Phone:(216) 445-9752
hardwaa@ccf.org
Fax:(216) 445-6269
laboratory

Daniel  Hettel B.S.
Daniel Hettel B.S.
HHMI Medical Student

Location:NB4-15
Phone:(216) 445-9752
hetteld@ccf.org
Fax:(216) 445-6269
laboratory

Hyun-Kyung   Ko Ph.D.
Hyun-Kyung Ko Ph.D.
Postdoctoral Fellow

Location:NB4-137
Phone:(216) 445-9751
koh@ccf.org
Fax:(216) 445-6269
laboratory

Jianneng  Li Ph.D.
Jianneng Li Ph.D.
Postdoctoral Fellow

Location:NB4-137
Phone:(216) 445-9751
lij7@ccf.org
Fax:(216) 445-6269
laboratory

Jeffrey  McManus Ph.D.
Jeffrey McManus Ph.D.
Postdoctoral Fellow

Location:NB4-137
Phone:(216) 445-9752
mcmanuj@ccf.org
Fax:(216) 445-6269
laboratory

Marianne  Petro B.S.
Marianne Petro B.S.
Lead Research Technologist

Location:NB4-137
Phone:(216) 445-9751
petrom@ccf.org
Fax:(216) 445-6269
laboratory

Madhumita  Pradhan Ph.D.
Madhumita Pradhan Ph.D.
Postdoctoral Fellow

Location:NB4-137
Phone:(216) 445-9751
pradham@ccf.org
Fax:(216) 445-6269
laboratory

Liang  Qin Ph.D.
Liang Qin Ph.D.
Postdoctoral Fellow

Location:NB4-25
Phone:(216) 445-9752
qinl@ccf.org
Fax:(216) 445-6269
laboratory

Ziqi  Zhu Ph.D.
Ziqi Zhu Ph.D.
Postdoctoral Fellow

Location:NB4-137
Phone:(216) 445-9751
zhuz@ccf.org
Fax:(216) 445-6269
laboratory


Hearn JW, AbuAli G, Reichard CA, Reddy CA, Magi-Galluzzi C, Chang KH, Carlson R, Rangel L, Reagan K, Davis BJ, Karnes RJ, Kohli M, Tindall D, Klein EA, Sharifi N. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol. 2016 Aug 26.  [Epub ahead of print]

Li, Z., Alyamani, M., Li, J., Upadhyay, S., Balk, S.P., Taplin, M-E., Auchus, R.J., Sharifi, N. Redirecting abiraterone metabolism to biochemically fine tune prostate cancer anti-androgen therapy.  Nature. 2016 May 25;533(7604):547-51.

Li, Z., Bishop, A., Alyamani, M., Garcia, J.A., Dreicer, R., Bunch, D., Liu, J., Upadhyay, S.K., Auchus, R.J., Sharifi, N. Conversion of abiraterone to D4A drives antitumor activity in prostate cancer. Nature. 2015 Jul 16;523:347-51.

Goodwin, J.F., Kothari, V., Drake, J.M., Zhao, S., Dylgjieri, E., Dean, J.L., Schiewer, M.J., McNair, C., Magee, M.S., Den, R.B., Zhu, Z., Graham, N.A., Vashisht, A.A., Wohlschlegel, J.A., Graeber, T.G., Davicioni, E., Sharifi, N., Witte, O.N., Feng, F.Y., Knudsen, K.E. DNA-PK mediated transcriptional regulation drives tumor progression and metastasis.  Cancer Cell. 2015 Jul 13;28(1):97-113.

Sharifi, N. Steroid receptors aplenty in prostate cancer. N Engl J Med. 2014  Mar 6;370(10):970-1.

Chang, K-H., Li, R., Kuri, B., Lotan, Y., Roehrborn, C.G., Liu, J., Vessella, R., Nelson, P., Kapur, P., Guo, X., Mirzaei, H., Auchus, R.J., Sharifi, N. A gain-of-function mutation in DHT synthesis in CRPC.  Cell. 2013 154(5):1074-84.

Chang, K-H and Sharifi, N.  Prostate cancer – from steroid transformations to clinical translation.  Nature Reviews Urology. 2012 Dec;9(12):721-4.

Li, R, Evaul, K, Sharma, KK, Chang, K-H, Yoshimoto, J, Liu, J, Auchus, RJ, Sharifi, N.  Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in CRPC. Clin Cancer Res. 2012 Jul 1;18(13):3571-9.

Chang, K-H, Papari-Zareei, Watumull, L, Zhao, YD, Auchus, RJ, Sharifi N. Dihydrotestosterone synthesis bypasses testosterone to drive CRPC. Proc Natl Acad Sci USA. 2011 Aug 16;108(33):13728-33.