Miriam Greenberg

Miriam Greenberg

Research

 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.

Education

• B.A., Biology, Reed College (1972)
• M.S., Microbiology, Loyola University (1975)
• Ph.D., Genetics, Albert Einstein College of Medicine (1980)
• Postdoc, Molecular Biology, Harvard University (1985)

Awards and grants

• 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

Selected publications

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.

Click here to see the complete list of Greenberg lab publications through NCBI.

Currently teaching

• Bio 6700 - Responsible Conduct of Research - 1.0 Credit

Courses taught

• Bio 1030 - Biology Today - 3.0 Credits
• Bio 6180/7180 - Membrane Biology - 3.0 Credits
• Bio 6330 - Principles and Applications of Biotechnology II - 3.0 Credits
• Bio 6540 - Principles of Genetic Analysis - 1.0 Credit
• The Middle East Experience: Israel and the West Bank (Study Abroad Program)