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Faculty Profile: Daniela Matei, MD, Diana, Princess of Wales Professor of Cancer Research

Jennie Lin, MD

Matei, also a professor of Medicine in the Division of Hematology and Oncology and of Obstetrics and Gynecology in the Division of Gynecologic Oncology, studies how ovarian cancer grows and devises treatments that exploit weaknesses unique to the cancer. Ovarian cancer is more deadly than other reproductive cancers: women with ovarian cancer often have few or mild symptoms until the disease is in an advanced stage, and therefore difficult to treat.

While Matei is relatively new to Feinberg, she has already published in high-profile journals, including the New England Journal of Medicine, and has established a wide network of colleagues reflecting her interdisciplinary work. 

What are your research interests?

My laboratory studies mechanisms of metastasis and novel therapeutics for ovarian cancer. The general theme is translation between bench and clinic, with laboratory research forming the foundation for clinical experiments.

A new focus of research in the laboratory is the characterization of unique traits and therapeutic vulnerabilities of cancer stem cells. We recently defined the metabolome of cancer stem cells as being enriched in unsaturated fatty acids which are generated in situ and provide distinct energetic substrate for these rare cells’ survival. We are dissecting the mechanisms by which the unsaturated fatty acids fuel cancer “stemness” and are studying whether targeting lipid desaturases could eliminate cancer stem cells residual after chemotherapy.

Additionally, the laboratory is studying DNA and RNA methylation as a key regulator of response to DNA damage. Some of our laboratory findings were translated to the clinic by using DNA methyl transferase inhibitors to re-sensitize platinum-resistant ovarian tumors to chemotherapy, or, more recently, to immunotherapy. We characterized the genome and epigenome of platinum resistant ovarian tumors using specimens collected from clinical trials designed and conducted by our group. An ongoing investigator-initiated clinical trial at Northwestern University uses a DNA hypomethylating agent as a priming agent for immune checkpoint inhibitor therapy in women with platinum resistant ovarian cancer. 

I have also been engaged in clinical research and serve as the principal investigator of many clinical trials testing novel therapies for ovarian cancer, including several cooperative group and National Cancer Institute-sponsored trials for gynecologic cancer.

What is the ultimate goal of your research?

The ultimate goal is to improve the outlook of women with chemotherapy-resistant ovarian cancer by bringing new treatments developed in the laboratory. If we could benefit one patient, all the effort would have been worthwhile. Fortunately, I think, we have already reached that goal.

What types of collaborations are you engaged in across campus (and beyond)?

I am a relatively new investigator at Northwestern, having started in January 2016. I found the community of investigators in the Robert H. Lurie Comprehensive Cancer Center of Northwestern University to be especially welcoming and in the short time that I have been here, I have established many collaborations, who are helping re-shape my research interests. For example, by collaborating with Dr. Bin Zhang in the Department of Medicine, we have expanded our reach to evaluate the impact of epigenetic modifiers on the immune landscape of tumors. Together, we have been successful obtaining new funding from the Department of Defense to allow studying tumor biopsies from women enrolled on a clinical trial using a novel hypomethylating agent in combination with an immune checkpoint inhibitor.

I’m also collaborating with Dr. Vadim Backman in the Center for Physical Genomics and Engineering, Dr. Marcus Peter in the Department of Medicine and Dr. Ramana Davuluri in the Department of Preventive Medicine and Northwestern University Clinical and Translational Sciences Institute (NUCATS). We are developing a new project characterizing transcription regulation in cancer stem cells. I also have active long-distance collaborations, with Drs. Ji-Xin Cheng at Boston University, Kenneth Nephew at Indiana University and David Nolte at Purdue University. The concept of team science is more important than ever, with cross-cutting research themes and intersecting technologies being the forces that drive science going forward. 

How is your research funded?

My laboratory received research funding from the National Cancer Institute, Department of Defense, U.S. Department of Veterans Affairs and other private cancer foundations such as the Ovarian Cancer Research Alliance, V-foundation, and others. Together with other clinical investigators in the Cancer Center, we were awarded a LAPS grant from the NCI this year to fund clinical research related to cooperative group trials.

Who makes up your research team and what role does each individual play in your research?

I am very fortunate to be leading a group of engaged young researchers. Dr. Horacio Cardenas has been with me for almost 10 years and he is the mentor who welcomes students and keeps them on task—the glue that keeps the lab together. Dr. Hao Huang and Yinu Wang are promising junior investigators who lead the efforts on epigenetic alterations in platinum resistant ovarian cancer models and in cancer stem cells. Two very productive graduate students, Yaqi Zhang and Guangyuan Zhao, bring technical precision, curiosity and strong analytic tools to the team.

Last, but not least, we welcome physicians in training to get a taste of laboratory work and incorporate this knowledge in the way they approach clinical practice in the future. For example, Dr. Mathew Cowan, a fellow in Gynecologic Oncology, completed his research project in the lab, helping develop a new methodology to identify immune cells subpopulation in the tumor microenvironment.

In addition, several team members have moved on to permanent positions during this past year; Dr. Salvatore Condello is now an assistant professor at Indiana University, Dr. Livia Sima is a senior scientist at the Institute of Biochemistry in Bucharest and Dr. Nikky Nwani has started a career in clinical research and drug development at the Lurie Cancer Center.

Where have you recently published papers?

Our work describing alterations in lipid metabolism in cancer stem cells was published in Cell Stem Cell in 2017. We publish consistently in American Association for Cancer Research (AACR) journals, such as Cancer Research, Clinical Cancer Research and Molecular Cancer Therapeutics.

This year, I am the lead author on a standard of care changing paper published in the New England Journal of Medicine. This paper presents results of a randomized international phase III trial that compared chemo-radiotherapy to chemotherapy for the treatment of locally advanced endometrial cancer. The results of NRG-GOG 0258 indicate that the combined modality regimen did not result in an improvement in recurrence-free survival, and that chemotherapy alone remains the standard of care for stage III uterine cancer.

The study confirms that chemotherapy alone should be the preferred treatment approach for this patient population, avoiding the long term toxicities associated with radiotherapy.