Zohar Sachs Lab

The Sachs Lab's goal is to identify molecular mechanisms of leukemia stem cell self-renewal in acute myeloid leukemia (AML). Since AML cells are highly heterogeneous, we specialize in the application of single-cell, high throughput technologies (including mass cytometry/CyTOF and single-cell RNA sequencing) and patient-derived xenografts and genetically engineered mouse models to address these research questions. We believe that this approach will identify effective therapeutic targets for this deadly disease.

zohar

Celebrating cancer 'ResearcHERS' and addressing the challenges

Publications

  1. Evolution of clonal dynamics and differential response to targeted therapy in a case of systemic mastocytosis with associated myelodysplastic syndrome. Yun HD, Antony ML, Linden MA, Noble-Orcutt KE, Eckfeldt CE, Ustun C, Nelson AC, Sachs Z. Leuk Res. 2020 Aug;95:106404. doi: 10.1016/j.leukres.2020.106404. Epub 2020 Jun 11. PMID: 32569927
  2. Karen Sachs, Aaron L. Sarver, Klara E. Noble-Orcutt, Rebecca S. LaRue, Marie Lue Antony, Daniel Chang, Yoonkyu Lee, Connor M. Navis, Alexandria L. Hillesheim, Ian R. Nykaza, Ngoc A. Ha, Conner J. Hansen, Fatma K. Karadag, Rachel J. Bergerson, Michael R. Verneris, Matthew M. Meredith, Matthew L. Schomaker, Michael A. Linden, Chad L. Myers, David A. Largaespada, Zohar Sachs. Single-cell gene expression analyses reveal distinct self-renewing and proliferating subsets in the leukemia stem cell compartment in murine acute myeloid leukemia. Cancer Res. 2020 Feb 1;80(3):458-470. doi: 10.1158/0008-5472.CAN-18-2932. Epub 2019 Nov 29. PMID: 31784425
  3. Cayci Z, Ozturk K, Ustun C, Omer AK, Dincer E, Sachs Z, Linden MA. Sarcoid-like histiocytic proliferations in lymphoma patients can be PET-avid and mimic recurrent disease. Clinical Lymphoma, Myeloma, and Leukemia. Accepted August 2019
  4. Noel BM, Ouellette SB, Marholz L, Dickey D, Navis C, Yang TY, Nguyen V, Parker SJ, Bernlohr D, Sachs Z, Parker LL. Multiomic Profiling of Tyrosine Kinase Inhibitor-Resistant K562 Cells Suggests Metabolic Reprogramming To Promote Cell Survival. J Proteome Res. 2019 Apr 5;18(4):1842-1856. doi: 10.1021/acs.jproteome.9b00028. Epub 2019 Feb 21. PMID: 30730747
  5. Gilles SR, Baughn LB, Schomaker ML, Courville EL, Nelson AC, Sachs Z. Buccal epithelial cells display somatic, bone marrow-derived CALR mutation. Blood Adv. 2017 Nov 16;1(25):2302-2306.  PMID:29296879 *Featured on the journal cover
  6. Baughn LB*, Sachs Z*, Noble-Orcutt KE, Mitra A, Van Ness BG, and Linden MA. Phenotypic and functional characterization of a bortezomib resistant multiple myeloma cell line by flow and mass cytometry. Leuk and Lymphoma. Aug;58(8):1931-1940. PMID:27981867. *co-first authors
  7. Gupta SD, Sachs Z.  Novel single-cell technologies in acute myeloid leukemia research. Transl Res. 2017. Nov;189:123-135. PMID:28802867
  8. Maus RLG, Jakub JW, Nevala WK, Christensen TA, Noble-Orcutt KE, Sachs Z, Hieken TJ, Markovic SN.  Human melanoma-derived extracellular vesicles regulate dendritic cells potentially enabling lymph node metastases. Front Immunol. 2017 Mar 29;8:358. PMID:28424693
  9. Csizmar CM, Kim DH, Sachs Z, The Role of the proteasome in AML. Blood Cancer Journal. 2016;6(12)e503. PMID: 27911437 PMCID: PMC5223148 DOI: 10.1038/bcj.2016.112 URL: http://www.nature.com/bcj/journal/v6/n12/full/bcj2016112a.html
  10. Moench L, Sachs Z, Aasen G, Dolan M, Dayton V, Courville EL. Double- and triple-hit lymphomas can present with immature features, including TdT expression, and create diagnostic challenges. Leukemia and Lymphoma. 2016;1-10 PMID: 26892631
  11. Sachs Z, Been RA, DeCoursin KJ, Nguyen HT, Mohd Hassan NA, Noble-Orcutt KE, Eckfeldt CE, Pomeroy EJ, Diaz-Flores E, Geurts JL, Diers MD, Hasz DE, Morgan KJ, MacMillan ML, Shannon KM, Largaespada DA, Wiesner SM. Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency. Haematologica. 2016;101(10):1190-1199. PMCID: 27418650 PMC5046648.
  12. Trottier BJ, Sachs Z, DeFor TE, Shune L, Dolan M, Weisdorf DJ, Ustun C, Warlick ED. Novel disease burden assessment predicts allogeneic transplantation outcomes in myelodysplastic syndrome. Bone Marrow Transplant. 2016;51(2):199-204.  PMCID:  PMC5319562
  13. Yun YS, Kim KH, Tschida B, Sachs Z, Noble-Orcutt KE, Moriarity B, Ai T, Ding R, Williams J, Chen L, Largaespada DA, Kim D. mTORC1 regulates immunoproteasome assembly for protein stress response and cell survival. Molecular Cell. 2016;61(4):625-639.  PMID 26876939.
  14. Kempema AM, Widen JC, Hexum JK, Andrews TE, Wang D, Rathe SK, Meece FA, Noble KE, Sachs Z, Largaespada DA, Harki DA. Synthesis and antileukemic activities of C1-C10-modified parthenolide analogues. Bioorg Med Chem. 2015 Aug 1;23(15):4737-45. 2015 May 30. PMID: 26088334
  15. Ustun C, Trottier BJ, Sachs Z, DeFor TE, Shune L, Courville E, Holtan SG, Dolan M, Weisdorf DJ, Warlick ED. Monosomal karyotype at the time of diagnosis or transplantation predicts outcomes of Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome. Biol Blood Marrow Transplant. 2015 Jan 22. S1083-8791(15)00051-8.PMID: 25620751
  16. Courville EL, Sachs Z, Linden MA. Standardized synoptic reports for plasma cell neoplasms: integration of laboratory and clinical data. . In: Plasma Cell Neoplasms: A morphologic, cytogenetic, and Immunophenotypic approach. Linden MA, McKenna RW, editors. New York, NY: Springer; 2015.
  17. Sachs Z, LaRue RS, Nguyen HT, Sachs K, Noble KE, Mohd Hassan NA, Diaz-Flores E, Rathe SK, Sarver AL, Bendall SC, Ha NA, Diers MD, Nolan GP, Shannon KM, Largaespada DA. NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia. Blood. 2014 Nov 20;124(22):3274-83. PMID: 25316678
  18. Fall DJ, Stessman H, Patel SS, Sachs Z, Van Ness BG, Baughn LB, Linden MA.  Utilization of translational bioinformatics to identify novel biomarkers of bortezomib resistance in multiple myeloma. J Cancer. 2014 Sep 21;5(9):720-7. PMID: 25368671.
  19. Liegel J, Courville E, Sachs Z, Ustun C. Use of sorafenib for post-transplant relapse in FLT3/ITD-positive acute myelogenous leukemia: maturation induction and cytotoxic effect. Haematologica. 2014 Nov;99(11):e222-4. PMID: 25015937.
  20. Lunde L, Chuang C, Linden M, Williams S, Sachs Z, Zuzan C, Young J, Ustun C. Lethal small bowel necrosis due to aspergillosis during acute promyelocitic leukemia induction. Am J Hematology 2013;88(4):329-332. PMID: 22791390.
  21. Linden MA, Bachanova V, Sachs Z, Young JA, Singleton TP, Ustun C. Transformed large B-cell lymphoma in rituximab-allergic patient with chronic lymphocytic leukemia after allogeneic stem cell transplant: successful treatment with ofatumumab. Leuk Lymphoma 2013 Jan;54(1):174-6. PMID 22568510.
  22. Sachs Z, Sharpless N, DePinho R, Rosenberg N.  p16Ink4a induces apoptosis during Ab-MLV transformation of pre-B cells.  J Virol. 2004;78(7):3304-11. PMI:  9789064. PMCID:  PMC 23757.
  23. Mostecki J, Halgren A, Radfar A, Sachs Z, Ravitz J, Thome KC, Rosenberg N.  Loss of heterozygosity at the Ink4a/Arf locus facilitates Abelson virus transformation of pre-B cells. J Virol 2000;74(20):9479-87. PMID:  11000217.  PMCID:  PMC 112377.
  24. Berretta S, Sachs Z, Graybiel AM.  Cortically driven Fos in the striatum is amplified by local dopamine D2-class receptor blockade. Eur J Neurosci. 1999;11:4309-19. PMID 10594656.

MyNCBI Bibliography 12/17/19

https://www.ncbi.nlm.nih.gov/myncbi/zohar.sachs.1/bibliography/public/

Sachs Lab Members

Image of Sach's Lab Members

Sachs lab presenting new research findings (“Cell type-specific effects of crizotinib in human acute myeloid leukemia with TP53 alterations”) at the 2019 society for hematology (ASH) annual meeting in Orlando, FL. 

Left to right: Jeff Jensen, MD/PhD (former post-doc), Marie Lue Antony, PhD (post-doc), Klara Noble-Orcutt, MS (lab manager), and Zohar Sachs, MD/PhD (principal investigator)

Marie Lue Antony, PhD, Research Associate

Image of Marie Lue Antony

Research Interests: Cancer stem cells, AML
Current Research: Therapeutic targeting of leukemia stem cells in AML; understanding the therapeutic vulnerabilities of TP53 altered AML

Yoonkyu (Ryan) Lee, Graduate Student, PhD Candidate, Bioinformatics and computational biology program (BICB)

Image of Yoonkyu (Ryan) Lee

Research Interests: Cancer, single cell RNA-seq, genomics and machine learning
Current Research: I am developing new computational methods to analyze single cell RNA sequencing data to discover new features and dependencies of self-renewal
Education: BS, Biochemistry, University of Wisconsin (2016)
Email: leex5085@umn.edu

Daniel Chang, Graduate Student, PhD Candidate, Bioinformatics and computational biology program (BICB)

Image of Daniel Chang

Research Interests: Applying machine learning methods to single-cell RNA sequencing data, cancer stem cell self-renewal mechanisms, and statistical modeling of signaling
Current Research: Using a myelodysplastic syndromes (MDS) mouse model to study the transformation from MDS to secondary acute myeloid leukemia.
Education: BS, Microbiology, University of Minnesota (2013)

Klara Noble-Orcutt, MS, Lab Manager

Image of Klara Noble-Orcutt

Research Interests: Cancer stem cells, murine models of leukemia
Current Research: Defining therapeutic vulnerabilities in treatment resistant AML using patient-derived xenografts
Education: BS, MS, University of Minnesota
Email: noble116@umn.edu