Miriam L. Greenberg (aa3319)

Biological Sciences

Among the most exciting outcomes in the past two decades of biology research is the realization that lipids are key players not only in membrane structure and energy production, but in the regulation of membrane proteins, signal transduction, vesicular trafficking, secretion, and cytoskeletal rearrangements. Thus, it is not surprising that perturbation of lipid metabolism leads to a wide spectrum of pathologies, ranging from cancer to cardiovascular and neurological disorders. Sophisticated analytical technology has revealed that each class of lipids is characterized by extensive structural diversity with the potential to mediate numerous cellular processes. Elucidating the specialized functions of lipids is the next frontier in biology research.

In the Greenberg laboratory, we utilize the powerful genetic, molecular, and cell biological tools of the yeast system and relevant mammalian cell cultures to elucidate the cellular functions of two essential lipid pathways. One project is to understand the mitochondrial and cellular functions of cardiolipin, the signature lipid of the mitochondrial membrane. The second project seeks to elucidate the essential functions of inositol phospholipids and metabolites and the cellular consequences of inositol depleting drugs. These studies have implications for understanding the pathology underlying cardiovascular disorders and the therapeutic mechanisms of action of drugs used in the treatment of psychiatric disorders.

Mentoring in the Greenberg lab. The Greenberg lab has successfully mentored 29 students to the completion of the Ph.D. degree. Almost all have gone on to do postdoctoral research, and many are now independent scientists in academia, research institutes, or government regulatory agencies. Mentoring students is a primary focus of my lab and involves the following components:

Achieving independence. Becoming an independent investigator is arguably the most important goal of the Ph.D. program. To this end, I encourage my students to design their own experiments and troubleshoot the problems that inevitably arise. Initially, I help students a great deal in experimental design and suggested experiments, but I expect them to be fully independent by graduation. This goal is facilitated by formal monthly one-on-one meetings as well as informal meetings, in which the student’s creative input increases over time. Students must acquire expertise in cutting-edge approaches and technologies. In addition, I encourage my students to collaborate and interact with other scientists who have complementary expertise and utilize approaches that strongly contribute to the impact of their research.

Weekly lab meetings. During weekly lab meetings, a single individual presents her/his work and all lab members participate in discussions of the data, generally contributing helpful and often innovative suggestions. Scientific criticism is delivered in a supportive environment. Presenters meet with me two days before lab meeting to review PowerPoint presentations. This meeting serves as an instructional tool for giving scientific presentations, a skill that is absolutely essential for a successful scientist.

Dissertation committee meetings. It is our department’s policy, with which I strongly agree, that Ph.D. students meet at least annually with their dissertation committees. These meetings are exceptionally useful in ensuring that students are on track, and in providing advice from committee members with diverse expertise. While students can thus obtain scientific advice and support, they are expected to achieve independence in the design and execution of experiments, and most important, in creatively guiding their research.

Participation in department and university initiatives. I encourage student participation in departmental seminar programs and in the university-wide program Lipids@Wayne (http://lipids.wayne.edu), of which I am a founder and co-organizer. These provide opportunities to present their work at the annual Lipids@Wayne Symposium and the Graduate Student and Postdoc Research Symposia on the main campus and School of Medicine.

Presentations at scientific conferences. I encourage and support student presentations at meetings, university symposia, and national and international conferences, which gives them the opportunity to both present their work and gain visibility in the scientific community. It also exposes them to the most cutting-edge research relevant to their interests. I expect them to prepare their formal talks in advance, and I observe and critique their practice sessions in the context of our lab meetings. In this way, each student has the opportunity to develop her/his presentation, while other lab members contribute and learn from the experience.

Publishing papers and developing writing skills. I expect my students to carry out research resulting in high quality first-author papers published in respected peer-reviewed journals. Writing is an essential component of research. To train my students in scientific writing, I provide opportunities for them to write invited review articles, and I require them to write their research manuscripts, although I play a major role in editing them. This always entails many drafts and an enormous input of energy in editing and discussion, but it is essential for the development of scientific writing skills.

Grant-writing skills. My training in grant-writing skills has several components. First, I believe in encouraging students and postdocs to obtain predoctoral grants. This is obviously beneficial to the lab, but it is greatly important to the student, as it enhances independence and provides an opportunity to learn to write a grant application. Second, I ask that students review and critique my own grant applications. In this manner, they can learn first-hand what is involved in the process. Third, I support student participation in grant writing seminars and workshops.

Responsible conduct in research. We have an obligation to the scientific community, to society and to ourselves to adhere to the professional and ethical standards in research. I currently teach BIO 6700: Responsible Conduct of Research, the goal of which is to explore the norms of ethical scientific behavior, standards of rigor and reproducibility in experimentation, the value and process of peer review and the impact of research on society. I believe this course is an essential component of the education of my students.

Mentorship commitment. Mentoring of graduate students in the laboratory and watching students become confident, independent, and accomplished scientists requires an awesome commitment. I respect the uniqueness of each student and realize that each must find her/his own way of working. In addition to the training approaches described above, I consider my commitment to my graduate students to be lifelong. Former students and postdocs who are now independent scientists continue to call me for advice and I am proud to help.

Awards

• WSU Academy of Scholars Inductee (2018)
• Weizmann Institute of Science Belkin Faculty Fellowship (2016-2017)
• WSU OVPR Faculty Postdoc Award (2014)
• WSU Board of Governors Distinguished Faculty Fellowship (2012-2013)
• WSU College of Science Teaching Award (2004)
• WSU Outstanding Graduate Mentor Award (2004)
• Neufeld Memorial Research Award, U.S. Israel Binational Science Foundation (2002)
• Dozor Fellowship, Ben Gurion University of the Negev, Israel (2000-2001)
• Nederlandse Organisatie voor Wetenschappelijk Onderzoek Fellowship (2000-2001)
• WSU Career Development Chair (1995-1996)

Current funding

• NIH – R01GM134715 – Controlling Monolysocardiolipin/Cytochrome c Peroxidase Complexes in Barth Syndrome
• NIH – R01HL117880 – The Role of Cardiolipin in the TCA Cycle: Implications for Barth Syndrome
• NIH – R01GM125082 – Novel Mechanisms of Regulation of Inositol Biosynthesis
• Barth Syndrome Foundation – Supplementation of critical metabolites improves TCA cycle function and viability of tafazzin-deficient cells
• AHA Predoctoral Fellowship (to Zhuqing Liang) – Frataxin deficiency in cardiolipin-deficient cells leads to defective Fe-S biogenesis

• Wayne State-led research helps uncover therapies for Barth Syndrome's deadly cardiac and skeletal effects
• Wayne State researcher receives $1.95 million NIH grant to study impact of inositol homeostasis on essential cellular functions

2020

• Salsaa M., Pereira B., Liu J., Yu W., Jadhav S., Hüttemann M., Greenberg M.L. Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae. Sci. Rep., 10:11785
• Li Y., Lou W., Grevel A., Böttinger L., Liang Z., Ji J., Patil V.A., Liu J., Ye C., Hüttemann M., Becker T., Greenberg M.L. Cardiolipin-deficient cells have decreased levels of the iron-sulfur biogenesis protein frataxin. J. Biol. Chem., 295:11928-11937
• Patil V.A., Li Y., Ji J., Greenberg M.L. Loss of the mitochondrial lipid cardiolipin leads to decreased glutathione synthesis. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids, 1865(2)

2019

• Xu Y., Anji M., Donelian A., Yu W., Greenberg M.L., Ren M., Owusu-Ansah E., Schlame M. Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin. PNAS, 116:11235-11240
• Li Y., Lou W., Raja V., Denis S., Yu W., Schmidtke M.W., Reynolds C.A., Schlame M., Houtkooper R.H., Greenberg M.L. Cardiolipin-induced activation of pyruvate dehydrogenase links mitochondrial lipid biosynthesis to TCA cycle function. J. Biol. Chem., 294:11568-11578
• Raja V., Salsaa M., Joshi A.S., Li Y., van Roermund C.W.T., Saadat N., Lazcano P., Schmidtke M., Hüttemann M., Gupta S.V., Wanders R.J.A., Greenberg M.L. Cardiolipin-deficient cells depend on anaplerotic pathways to ameliorate defective TCA cycle function. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids, 1864(5):654-661

2018

• Case K.C., Salsaa M., Yu W., Greenberg M.L. Regulation of Inositol Biosynthesis: Balancing Health and Pathophysiology. In: Handb. Exp. Pharmacol. Springer, Berlin, Heidelberg
• Yedulla N.R., Naik A.R., Kokotovich K.M., Yu W., Greenberg M.L., Jena B.P. Valproate inhibits glucose-stimulated insulin secretion in beta cells. Histochem Cell Biol, 150(4):395-401
• Lou W., Ting H.C., Reynolds C.A., Tyurina Y.Y., Tyurin V.A., Li Y., Ji J., Yu W., Liang Z., Stoyanovsky D.A., Anthonymuthu T.S., Frasso M.A., Wipf P., Greenberger J.S., Bayir H., Kagan V.E., Greenberg M.L. Genetic re-engineering of polyunsaturated phospholipid profile of Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the effects of cardiolipin peroxidation. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids, 1863(10):1354-1368
• Lou W., Reynolds C.A., Li Y., Liu J., Hüttemann M., Schlame M., Stevenson D., Strathdee D., Greenberg M.L. Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids, 1863(8):857-865

See the complete list of Greenberg lab publications through NCBI.