Sanaz Memarzadeh, M.D., Ph.D.

Laboratory Address:
610 Charles E. Young Drive East
3017 Terasaki Life Sciences Building
Los Angeles, CA 90095

Office Address:
200 Medical Plaza, Suite 220
Los Angeles, CA 90095

Affiliations
Affiliations
Professor, Obstetrics and Gynecology
Member, Gynecologic Oncology, Cell & Developmental Biology GPB Home Area, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Gynecologic Endoscopy, JCCC Cancer and Stem Cell Biology Program Area, Molecular Pharmacology GPB Home Area
Research Interests

The overarching theme of my research is overcoming mechanisms of therapy resistance in gynecologic cancers. As a clinician-scientist, my career goal is to develop more effective and less toxic therapies for women impacted by these tumors. We are making progress in this woefully understudied area by discovering the molecular and cellular underpinnings of these cancers and exploiting existing vulnerabilities pharmacologically. Our discoveries have broad applications to cancer treatment in general and we hope to move them into clinical trials. 

 

A. Characterizing and profiling therapy resistant ovarian cancer tumor cells

Ovarian cancer has an annual incidence of about 22,000 cases in the United States. Carboplatin, a platinum-based chemotherapy, is the frontline treatment. Patients respond to this treatment initially, but experience relapse with therapy-resistant disease. The inability to predict response to carboplatin poses a clinical challenge. Patients are classified as having resistant disease after the tumor fails to respond or when relapse of disease occurs within 6 months of its administration. At this point, non-platinum based standard chemotherapies (Taxol, topotecan, and Doxil), or biologic agents (such as bevacizumab) are used with limited response. Given this clinical challenge, national guidelines recommend enrolling patients with platinum-resistant ovarian cancer into clinical trials. Rational design of these trials, which will entail testing combination therapies, require understanding unique therapeutic vulnerabilities in platinum-resistant ovarian cancer cells.

To understand the emergence of platinum-resistance in ovarian cancer, we are focused on identifying the unique antigenic signature of therapy-resistant ovarian cancer cells using cyTOF. A large panel of antigens is being investigated across different ovarian cancer cell lines and primary patient tumor samples. This may potentially lead to identification of biomarkers that may be utilized to predict a patient’s response to platinum-based chemotherapy. In parallel, we are utilizing an in vitro 3D miniring organoid assay to test the platinum sensitivity of patient ovarian cancer tumor samples. This may be adopted as a potential tool to predict chemotherapy response of the patients before drug administration.

Most chemoresistance studies in ovarian cancer are also limited by lack of a suitable in vivo models that can recapitulate the evolution of ovarian cancer cells during the course of chemotherapy. To address this problem, we are developing in vivo models using platinum-resistant patient-derived xenografts (PDX) to model the disease starting from proliferative cells to recurrent cells after platinum treatment. This research approach will offer a unique opportunity to investigate the therapy-induced changes in cancer cells using genetic and proteomic analyses.

 

B. Therapeutic targeting of platinum resistant gynecologic and ovarian cancer tumor cells

Resistance to platinum-based chemotherapy poses a significant clinical challenge for the treatment of patients diagnosed with aggressive gynecologic cancers. Development of platinum resistance is a complex and multifaceted process. We are investigating two potential reasons for therapy resistance in the laboratory: (1) overexpression of inhibitors of apoptosis proteins (IAPs) which can promote cancer cell survival by blocking apoptosis, and (2) alterations in the tumor suppressor p53 commonly found in aggressive gynecologic tumors. To address these two potential mechanisms that may mediate therapy resistance, we are investigating whether degradation of IAPs using a small molecule inhibitor can sensitize platinum-resistant ovarian cancer cells to the cytotoxic effects of carboplatin. In addition, we are investigating the efficacy of a structure-based peptide, called ReACp53, in targeting p53-mutated tumors of the gynecologic tract. We are testing if such combination therapies can better target ovarian cancer tumor cells.

 

C. Studying interactions between epithelia and stroma in normal and cancerous tissue.

Estrogen drives endometrial carcinogenesis and the progesterone hormone opposes this effect. As a first step, to gain mechanistic insight into stromal vs. epithelial signals that may modulate hormonal sensitivity, we established an endometrial cancer preclinical model. The power of this system is that we can independently induce genetic changes in epithelium or stroma in order to accurately recapitulate mutational patterns occurring in human tumors. Using this model we found that deletion of PTEN in endometrial epithelia can initiate endometrial cancers that closely resemble human disease and progesterone hormone anti-tumor effects may be mediated through the stroma. In studying human samples we learned that levels of progesterone receptor expression in stroma could correlate with response to progesterone therapy in endometrial hyperplasia and cancer.

 

D. Ongoing collaborations

We are fortunate to collaborate with a multidisciplinary team of scientists at UCLA.

 

Ongoing collaboration with Dr. Lili Yang

Research focus: investigating strategies that may increase the ability of the body’s immune system to fight ovarian cancer

 

Ongoing collaboration with Dr. Thomas Graeber 

Research focus: investigating the genetic profile of tumor cells before and after administration of chemotherapy to better understand mechanisms of therapy resistance

 

Ongoing collaboration with Dr. Owen Witte

Research focus: understanding genetic alterations that can transform normal human gynecologic tissues

 

Ongoing collaboration with Drs. Zoran Galic and Alex Garcia 

Research focus: understanding the identity of therapy resistance tumor cells using CyTOF

Biography

Dr. Sanaz Memarzadeh is a board certified clinician-scientist. In the clinic she is a highly skilled cancer surgeon and cares for women with gynecologic cancers (ovarian, endometrial, vulvar, cervical and tubal cancers). In the laboratory, she is the director of the G.O. Discovery Laboratory team. She has an eye for research that is immediately applicable and translatable to patient care. In fact, every question asked in her laboratory is a biologic question born out of an important yet unanswered question from the clinic. She and her team thrive on doing research that will impact lives of patients from bench to bedside and back. The NIH, the American Cancer Society, the Veterans Administration, and several foundations including The Ovarian Cancer Circle/Inspired by Robin Babbini have helped fund her work. She also has collaborations with the community to raise awareness and funds for women’s cancer research. She is the recipient of multiple awards including an APGO excellence in teaching award and the Los Angeles City Council recognition for commitment to ovarian cancer research to name a few. One of her major goals is to help train the next generation of scientists that will help revolutionize medicine as practiced today. 

Publications

A selected list of publications:

Phan Nhan, Hong Jenny J, Tofig Bobby, Mapua Matthew, Elashoff David, Moatamed Neda A, Huang Jin, Memarzadeh Sanaz, Damoiseaux Robert, Soragni Alice   A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids Communications biology, 2019; 2: 78.
Neal Adam S, Nunez Miguel, Lai Tiffany, Tosevska Anela, Morselli Marco, Amneus Malaika, Zakhour Mae, Moatamed Neda A, Pellegrini Matteo, Memarzadeh Sanaz   Expression of Stromal Progesterone Receptor and Differential Methylation Patterns in the Endometrium May Correlate with Response to Progesterone Therapy in Endometrial Complex Atypical Hyperplasia Reproductive sciences (Thousand Oaks, Calif.), 2020; .
Soragni Alice, Janzen Deanna M, Johnson Lisa M, Lindgren Anne G, Thai-Quynh Nguyen Anh, Tiourin Ekaterina, Soriaga Angela B, Lu Jing, Jiang Lin, Faull Kym F, Pellegrini Matteo, Memarzadeh Sanaz, Eisenberg David S   A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas Cancer cell, 2016; 29(1): 90-103.
Tiourin Ekaterina, Velasco Victor S, Rosales Miguel A, Sullivan Peggy S, Janzen Deanna M, Memarzadeh Sanaz   Tubal Ligation Induces Quiescence in the Epithelia of the Fallopian Tube Fimbria Reproductive sciences (Thousand Oaks, Calif.), 2015; .
Janzen Deanna M, Paik Daniel Y, Rosales Miguel A, Yep Brian, Cheng Donghui, Witte Owen N, Kayadibi Huseyin, Ryan Christopher M, Jung Michael E, Faull Kym, Memarzadeh Sanaz   Low Levels of Circulating Estrogen Sensitize PTEN-null Endometrial Tumors to PARP Inhibition In Vivo Molecular cancer therapeutics, 2013; .
Janzen Deanna M, Rosales Miguel A, Paik Daniel Y, Lee Daniel S, Smith Daniel A, Witte Owen N, Iruela-Arispe M Luisa, Memarzadeh Sanaz   Progesterone receptor signaling in the microenvironment of endometrial cancer influences its response to hormonal therapy Cancer research, 2013; .
Paik Daniel Y, Janzen Deanna M, Schafenacker Amanda M, Velasco Victor S, Shung May S, Cheng Donghui, Huang Jiaoti, Witte Owen N, Memarzadeh Sanaz   Stem-Like Epithelial Cells are Concentrated in the Distal End of the Fallopian Tube: A Site for Injury and Serous Cancer Initiation Stem cells (Dayton, Ohio), 2012; .
Cai Houjian, Memarzadeh Sanaz, Stoyanova Tanya, Beharry Zanna, Kraft Andrew S, Witte Owen   Collaboration of Kras and Androgen receptor signaling stimulates EZH2 expression and tumor propagating cells in prostate cancer Cancer research, 2012; .
Janzen Deanna M, Cheng Donghui, Schafenacker Amanda M, Paik Daniel Y, Goldstein Andrew S, Witte Owen N, Jaroszewicz Artur, Pellegrini Matteo, Memarzadeh Sanaz   Estrogen and progesterone together expand murine endometrial epithelial progenitor cells Stem cells (Dayton, Ohio), 2012; 31(4): 808-22.
Memarzadeh Sanaz, Cai Houjian, Janzen Deanna M, Xin Li, Lukacs Rita, Riedinger Mireille, Zong Yang, DeGendt Karel, Verhoeven Guido, Huang Jiaoti, Witte Owen N   Role of autonomous androgen receptor signaling in prostate cancer initiation is dichotomous and depends on the oncogenic signal Proceedings of the National Academy of Sciences of the United States of America, 2011; 108(19): 7962-7.
Cai Houjian, Smith Daniel A, Memarzadeh Sanaz, Lowell Clifford A, Cooper Jonathan A, Witte Owen N   Differential transformation capacity of Src family kinases during the initiation of prostate cancer Proceedings of the National Academy of Sciences of the United States of America, 2011; 108(16): 6579-84.
Lukacs Rita U, Memarzadeh Sanaz, Wu Hong, Witte Owen N   Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation Cell stem cell, 2010; 7(6): 682-93.
Memarzadeh Sanaz, Zong Yang, Janzen Deanna M, Goldstein Andrew S, Cheng Donghui, Kurita Takeshi, Schafenacker Amanda M, Huang Jiaoti, Witte Owen N   Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium Proceedings of the National Academy of Sciences of the United States of America, 2010; 107(40): 17298-303.
Lawson Devon A, Zong Yang, Memarzadeh Sanaz, Xin Li, Huang Jiaoti, Witte Owen N   Basal epithelial stem cells are efficient targets for prostate cancer initiation Proceedings of the National Academy of Sciences of the United States of America, 2010; 107(6): 2610-5.
Nosov Vladimir, Park Susan, Rao Jianyu, Memarzadeh Sanaz   Non-Peutz-Jeghers syndrome associated ovarian sex cord tumor with annular tubules: a case report Fertility and sterility, 2009; 92(4): 1497.e5-8.
Memarzadeh Sanaz, Xin Li, Mulholland David J, Mansukhani Alka, Wu Hong, Teitell Michael A, Witte Owen N   Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor Cancer Cell, 2007; 12(6): 572-85.
Memarzadeh S, Lee S B, Berek J S, Farias-Eisner R   CA125 levels are a weak predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2004; 13(2): 120-4.
Memarzadeh S, Holschneider C H, Bristow R E, Jones N L, Fu Y S, Karlan B Y, Berek J S, Farias-Eisner R   FIGO stage III and IV uterine papillary serous carcinoma: impact of residual disease on survival International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2004; 12(5): 454-8.
Memarzadeh Sanaz, Natarajan Sathima, Dandade Dipika P, Ostrzega Nora, Saber Peter A, Busuttil Ashley, Lentz Scott E, Berek Jonathan S   Lymphovascular and perineural invasion in the parametria: a prognostic factor for early-stage cervical cancer Cancer Cell, 2003; 102(3): 612-9.
Ide Hisamitsu, Seligson David B, Memarzadeh Sanaz, Xin Li, Horvath Steve, Dubey Purnima, Flick Maryann B, Kacinski Barry M, Palotie Aarno, Witte Owen N   Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression Proceedings of the National Academy of Sciences of the United States of America, 2002; 99(22): 14404-9.
Memarzadeh Sanaz, Kozak Katherine R, Chang Lisbeth, Natarajan Sathima, Shintaku Peter, Reddy Srinivasa T, Farias-Eisner Robin, Memarzedeh Sanaz   Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer Proc. Natl. Acad. Sci. U.S.A, 2002; 99(16): 10647-52.
Memarzadeh S, Berek J S   Advances in the management of epithelial ovarian cancer The Journal of reproductive medicine, 2001; 46(7): 621-9; discussion 629-30.
Behboo R, Carroll P B, Memarzadeh S, Zeevi A, Conrad B, Rastellini C, Rao A S, Ricordi C   Improved long-term culture of functional human islets in serum-free medium Transplantation proceedings, 1994; 26(6): 3301.