Ilana Chefetz - The Hormel Institute

Ilana Chefetz Ph.D
Assistant Professor

Cancer Stem Cells & Necoptosis

Biography

Ilana Chefetz Menaker obtained her Bachelor’s degree in Food Engineering and Biotechnology from Technion. Ilana earned a PhD with Eli Sprecher working on rare dermatology disorder, Familial Tumoral Calcinosis. As a graduate student she was awarded Neeman Excellence Scholarship and Technion Woman Excellence Scientist Prize to continue for postdoctoral studies abroad.

After finishing her PhD Ilana joined the laboratory of Gil Mor at Yale Medical School where she was awarded three-year Life Science Postdoctoral Fellowship and was a recipient of 2010 AACR Scholar-in-Training Award. After a Postdoctoral position with Dr. Gil Mor at Yale, Dr. Chefetz moved to the University of Michigan Comprehensive Cancer Center to work with Dr. Ron Buckanovich. Her research there focused on developing novel therapeutics which target ALDH, an enzyme specifically expressed in chemotherapy resistant cancer stem-like cells. At University of Michigan Ilana received Ann and Sol Schreiber Mentored Investigator award, Foundation for Women’s Cancer WeRoc Research grant, and Marsha Rivkin Center for Ovarian Cancer Pilot Award. In addition, Dr. Chefetz was awarded University of Michigan 2015 Outstanding postdoctoral fellow prize, and in 2016 was promoted to a Research Assistant Professor position.

Education

Postdoctoral Fellowship
Yale University, Department of Medicine, New Haven, CT.
Life Science Foundation Postdoctoral Fellow in Molecular Oncology. Research topic: “Identification and characterization of ovarian cancer stem cells”, supervisor Prof. Gil Mor.
Ph.D.
Technion, Department of Medicine, Haifa, Israel
Genetics and Molecular Dermatology. Research topic: “Pathomechanisms of Hyperphosphatemic Familial Tumoral Calcinosis”, supervisor Prof. Eli Sprecher.
B.SC
Technion, Department of Biotechnology and Food Engineering, Haifa, Israel
B.Sc. in Food Engineering and Biotechnology

Awards

The Joseph S. & Caroline Gruss Life Monument Fund for assistance to IDF
ex-servicemen
HIAS Scholarship Award – in recognition of outstanding academic achievement
Albert Kligman Travel Fellowship – 68th Annual meeting of the Society for Investigative Dermatology, Los Angeles
ESDR Travel Fellowship – 37th Annual ESDR Meeting, Zurich, Switzerland
Neeman Travel Fellowship – 37th Annual ESDR Meeting, Zurich, Switzerland, 2007
Youth Travel Fund, FEBS course on “Structural variations in genome, gene expression, Single cell analysis: Arrays, Beads, High-throughput sequencing”, Prague, Czech Republic
ECCB Travel Fellowship – European Conference on Computational Biology, Cagliari, Italy
EFS Travel Bursary-3rd EFS Functional Genomics Conference, Innsbruck, Austria
Brozman Foundation Postdoctoral Award in Ovarian Cancer Research
Young Scientist Program Travel Fellowship 21st IUBMB & 12th FAOBMB International Congress of Biochemistry and Molecular Biology, Shanghai China
American Association for Cancer Research Scholar-in-Training Award
Tony B Academic Travel Award SLAS Washington DC
Top 5 Student Posters Student Award SLAS Washington DC
WeRoc Ovarian Cancer Research Grant Foundation for Women’s Cancer
Marsha Rivkin Ovarian Cancer Pilot Grant Rivkin Center for Ovarian Cancer
Geri Fournier Ovarian Cancer Research Grant Michigan Ovarian Cancer Alliance
Elsa U. Pardee Foundation grant
Liz Tilberis Career Development Grant Ovarian Cancer Research Foundation
Michigan-Israel Partnership for research and Education (declined due to move to Minnesota)

Institution

President Excellence Award, Technion
Dean Excellence Award, Technion
Neeman Excellence Scholarship for Ph.D. students, Technion
Short Term Fellowship: Thomas Jefferson University, Division of Rheumatology, USA
Department of Internal Medicine Annual Meeting 2013, Winner Plenary Poster section, University of Michigan
Department of Internal Medicine Annual Meeting, Winner Oral Plenary speaker, University of Michigan
Outstanding Postdoctoral Fellow Award University of Michigan

Professional memberships

AACR – American Association for Cancer Research
International Gynecologic Cancer Society

Research Interests

Ovarian cancer
Cancer Stem cells
Cell programmed necrosis (necroptosis)
Novel targeted therapies
Overcoming resistance in recurrent ovarian cancer
Necroptosis and downstream molecular and metabolic factors

Publications

1. Chefetz I., Alvero AB., Holmberg JC., Lebowitz N., Craveiro V.,Yang-Hartwich Y., Yin G., Squillace L.,, Gurrea Soteras M.,, Aldo P., Mor G. 2013. TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle (5.4). 12 (3).
2. Yin G., Alvero AB., Craveiro V., Holmberg JC., Fu H., Montagna M., Yang Y., Chefetz-Menaker I., Nuti S., Rossi M., Silasi D., Rutherford T., Mor G. 2013. Constitutive Proteasomal Degradation of TWIST-1 in Epithelial Ovarian Cancer Stem Cells Impacts Differentiation and Metastatic Potential . Oncogene (7.414). 32(1):39-49.
3. Chefetz I., Holmberg J., Alvero AB.,Visintin I., Mor G. 2011. Inhibition of Aurora-A Kinase Induces Cell-Cycle Arrest in Epithelial Ovarian Cancer Stem Cells by Affecting NFĸB Pathway. Cell Cycle (5.4). 10 (13).
4. Mor G., Ying G., Chefetz I., Yang Y., Alvero A. 2011. Ovarian cancer stem cells and inflammation. Cancer Biol Ther (2.907). 11(8): 708-13.
5. Gok F., Chefetz I., Indelman M., Kocaoglu M., Sprecher E. 2009. New mutations in GALNT3 cause autosomal recessive hyperostosis-hyperphosphatemia syndrome. Acta Orthop (1.9), 80(1)131-4.
6. Gonen R., Shahar R., Grimpel Y., Chefetz I., Sammar M., Meiri H., Gibor Y. 2008. Early prediction of pre-eclampsia with PP13: a longitudinal study. BJOG (3.35). 115(12):1465-72.

7. Chefetz I., Sprecher E. 2009. Familial tumoral calcinosis and the role of O-glycosylation in the maintenance phosphate homeostasis. Biochim Biophys Acta (5.016). 1792(9):847-52.
8. Chefetz I., Kohno K., Uitto J., Richard G., Sprecher E. 2009. GALNT3, a gene associated with HFTC, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity. Biochim Biophys Acta (5.016). 1792(1):61-67.
9. Huppertz B., Sammar M., Chefetz I., Neumaier-Wagner P., Bartz C., Meiri H. 2008. Longitudinal Determination of Serum PP13 during Development of Preeclampsia. Fetal Diagnosis and Therapy (1.18). 24(3):230-236.
10. Romero R., Kusanovich J., Than N., Erez, O., Chefetz I., Meiri H., Tal Y., Cuckle H. 2008. First-trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol (3.313). 199(2):122.e1-122.e11.
11. Hershkovitz D., Mandel H., Ishida-Yamamoto A., Chefetz I., Hino B., Luder A., Indelman M., Bergman R., Sprecher E. 2008. Defective lamellar granule secretion in Arthrogryposis, Renal dysfunction and Cholestasis (ARS) syndrome caused by a mutation in VPS33B. Arch Dermatol (4.23). 144(3):334-40.
12. Chefetz I., Amitai D., Adir N., Topaz O., Indelman M., Bergman R., Uitto J., Richard G., Sprecher E. 2008. Normophosphatemic Familial Tumoral Calcinosis is caused by loss-of-function mutation in SAMD9, encoding a TNF-α responsive protein. Journal of Investigative Dermatology (6.270). 128(6):1423-9.
13. Chefetz I., Sammar M., Gibor Y., Meiri H., Cucckle H., Myles W. 2007. First-trimester PP13 screening for preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol (3.313). 197 (1): 35.e1-7.
14. Spencer K., Cowans N., Chefetz I., Tal J., Kuhnreich I., Meiri H. 2007. Second-trimester uterine artery Doppler pulsatility index and maternal serum PP13 as markers of pre-eclampsia.
Prenat Diagn (2.152). 27(3):258-63.
15. Spencer K., Cowans N., Chefetz I., Tal J., Meiri H. 2007. First trimester maternal serum PP13, PAPP-A and second trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol (3.163). 29(2): 128-134.
16. Topaz O., Indelman M., Chefetz I., Geiger D., Metzker A., Altschuler Y., Sprecher E. 2006. A Deleterious mutation in SAMD9 causes Normophosphatemic Familial Tumoral Calcinosis. Am. J. Hum Genet (11.68). 79(4): 759-764.
17. Nicolaides K., Bindra R., Turan O., Chefetz I., Sammar M., Cuckle H. 2006. A novel approach to first-trimester screening for early pre-eclampsia combining serum PP13 and Doppler Ultrasound. Ultrasound Obstet Gynecol (3.163). 27(1):13-17.
18. Chefetz I., Heller R., Indelman M., Topaz O., Bergman R., Sprecher E., Schoenau E. 2005. A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification. Hum Genet (5.047). 118(2):261-266.
19. Sprecher E., Topaz O., Chefetz I., Bergman R., Mandel H. 2005. A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis and palmoplantar keratoderma. Am. J. Hum Genet (11.68). 77(2):242-51.

Contact Information

Primary Research Areas

Our lab studies the molecular and metabolic aspects of cell programmed necrosis (necroptosis) in order to design targeted therapies and prevent recurrent disease. Cell programmed necrosis or necroptosis is a recently identified novel regulated cell death pathway. Cell death with necrotic morphology and features though to be a non-regulated and uncontrollable event associated with cell injury, inflammation or ischemia. However, recent studies now reveal that necrosis can occur in regulated manner. Necroptosis participates in pathogenies of diseases including neurodegeneration, ischemia and heart disorders, and viral infections; thus targeting necroptosis will prevent or mitigate undesirable cell death. On the other hand, drugs, inducing necroptotic cell death in tumors, can potentially overcome drug resistance in cancer cells due to elevated expression of anti-apoptotic proteins. Thus, elucidation of necroptosis/cell proliferation or necroptosis/apoptosis balance is essential to trigger cancer cell death or prevent pathological conditions such as ischemia or inflammation. The most studied kind of necroptosis is initiated by TNF-α while Caspases are inhibited using pan-Caspase inhibitor ZVAD-FMK, requires the kinase activity of Receptor-interacting proteins 1 and 3 (RIPK1 and RIPK3) followed by their downstream target MLKL. Necroptosis execution involves formation of micro-complex (20 MDa) necroptosome followed by disintegration of mitochondrial and plasma membranes. Despite necroptosis importance, many molecular downstream events are unknown or being disputed.