Mikhail Nikiforov


About Mikhail Nikiforov


Mikhail A. Nikiforov, PhD, came to the Department of Cell Stress Biology at Roswell Park Comprehensive Cancer Center in December 2007 as an Associate Member and Associate Professor of Oncology. Dr. Nikiforov’s research program is focused on several aspects of molecular biology and drug resistance of melanoma and several blood malignancies including:

  1. Elucidation of molecular mechanisms underlying oncogene-dependent senescence in normal human melanocytes and metastatic phenotypes in melanoma cells.
  2. Understanding the mechanisms by which oxidative stress promotes oncogene-induced senescence and suppresses melanoma metastasis.
  3. Acquisition of invasive phenotypes by melanoma cells.
  4. Discovery of novel prognostic markers of melanoma.
  5. The role of Krüppel-like transcription factors in the regulation of therapeutic outcomes in multiple myeloma, acute promyelocytic leukemia, and acute myeloid leukemia.

In parallel, Dr. Nikiforov’s lab is actively pursuing the development of a novel class of small molecule inhibitors of C-MYC, an oncogenic transcription factor that is overexpressed in more than 80% of human cancers. Dr. Nikiforov’s research is funded by the National Cancer Institute, and American Cancer Society.


Roswell Park Comprehensive Cancer Center

  • Adjunct Faculty
  • Department of Cell Stress Biology


Education and Training:

  • 1997 - PhD - Genetics, University of Illinois at Chicago
  • 1992 - BS/MS - Biochemistry, Moscow State University, Moscow, Russia


  • 1997-2000 - Postdoctoral Fellow - Department of Biology, University of Rochester

Professional Experience:

  • 2004-2007 - Assistant Professor - Department of Dermatology, University of Michigan
  • 2000-2004 - Research Associate - Department of Molecular Biology, Princeton University


Research Overview:

Mechanisms of Melanoma Progression

Malignant melanoma is one of the most aggressive types of human cancers. Currently, the median survival time of metastatic melanoma patients is approximately 8.5 months. In the skin, melanoma often originates from nevi which represent benign aggregates of senescent (permanently arrested) melanocytes. Thus, melanomas that originate from nevi must have developed mechanisms to overcome senescence, and these mechanisms are largely unknown. Recently, my lab has established that the overexpression of oncogenic transcription factor C-MYC significantly suppresses senescence in normal melanocytes. Reciprocally, the depletion of C-MYC in human metastatic melanoma cells re-activated dormant senescence programs, indicating that C-MYC is continuously required for the suppression of senescence during melanoma progression. The mechanisms that are required for the suppression of senescence by C-MYC in normal human melanocytes and melanoma cells are currently being pursued in my laboratory.

Invasion is one of the most detrimental features of melanoma. During the past several years, we found that C-MYC positively regulates melanoma cell invasion, although the mechanisms are not known. These mechanisms are also being investigated in my lab.

Novel Agents for Melanoma Therapy

The poor prognosis of metastatic melanoma has been associated with exceptional resistance of this malignancy to available antineoplastic treatments, ranging from immunological approaches to radio- or chemotherapy. Thus, the development of novel anti-melanoma agents is a high priority for melanoma treatment. Elevated expression of the oncogene C-MYC has been associated with advanced stages of melanoma in several studies, including ours. By performing a multi-step screening of complex small molecule libraries, we have identified several compounds that efficiently and specifically suppress MYC-dependent transcriptional regulation in cells from all tested human tumor lines including metastatic melanomas. Moreover, one compound substantially decreased the growth of human melanoma xenografts in nude mice without any apparent side effects. Further development of the identified compounds into anti-melanoma chemotherapeutic agents is being pursued in my laboratory.

KLF9 - Novel Transcriptional Regulator of Multiple Myeloma Chemotherapy Resistance

Multiple myeloma (MM) is a plasma cell disorder that accounts for approximately 10% of all hematologic malignancies. Although the introduction of novel agents in the past decade has increased the median overall survival of myeloma patients from 30 months to 45-72 months, the disease remains incurable. One such agent, bortezomib (Velcade®, PS-341), significantly increased overall survival in patients with relapsed or refractory multiple myeloma. Bortezomib suppresses proteosomal degradation leading to substantial changes in cellular transcriptional programs and ultimately resulting in apoptosis. Transcriptional regulators that are required for bortezomib-induced apoptosis in MM cells are largely unknown.

Recently, our lab has discovered that a member of Kruppel-like family of transcription factors, KLF9, regulates bortezomib-induced apoptosis in MM cells. Suppression of KLF9 also induced resistance to another anti-myeloma agent, novel histone deacetylase inhibitor LBH589. We have shown that basal KLF9 levels are higher in MM cells from patients that responded to bortezomib compared to non-responders. Thus, KLF9 appears to be an important factor for drug-resistance in multiple myeloma. Molecular mechanisms of KLF9 functioning in MM and other blood malignancies are currently being studied in my laboratory.


Full Publications list on PubMed

Selected Publications:

  • Fink EE, Mannava S, Bagati A, Bianchi-Smiraglia A, Nair JR, Moparthy K, Lipchick BC, Drokov M, Utley A, Ross J, Mendeleeva LP, Savchenko VG, Lee KP, Nikiforov MA. Mitochondrial thioredoxin reductase regulates major cytotoxicity pathways of proteasome inhibitors in multiple myeloma cells. Leukemia. 2015 Jul 24. [Epub ahead of print]
  • Bianchi-Smiraglia A, Wawrzyniak JA, Bagati A, Marvin EK, Ackroyd J, Moparthy S, Bshara W, Fink EE, Foley CE, Morozevich GE, Berman AE, Shewach DS, Nikiforov MA. Pharmacological targeting of guanosine monophosphate synthase suppresses melanoma cell invasion and tumorigenicity. Cell Death and Differentiation. 2015 Apr 24. [Epub ahead of print]
  • Zucker SN, Fink EE, Bagati A. Mannava S, Bianchi-Smiraglia A, Bogner PN, Wawrzyniak JA, Foley C, Leonova KI, Grimm MJ, Moparthy K, Ionov Y, Wang J, Liu S, Bakin AV, Sexton S, Kandel ES, Zhang Y, Kaminski N, Segal BH, Nikiforov MA. Nrf2 amplifies oxidative stress via induction of Klf9. Molecular Cell. 2014; 53:916-928.
  • Wawrzyniak JA, Bianchi-Smiraglia A, Bshara W, Mannava S, Ackroyd J, Bagati A, Omilian AR, Im M, Fedtsova N, Miecznikowski JC, Moparthy KC, Zucker SN, Zhu Q, Kozlova NI, Berman AE, Hoek KS, Gudkov AV, Shewach DS, Morrison CD, Nikiforov MA. A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a suppressor of melanoma invasion. Cell Reports; 2013; 5(2):493-507.
  • Mannava S, Zhuang D, Nair JR, Bansal R, Wawrzyniak JA, Zucker SN, Fink EE, Moparthy KC, Hu Q, Liu S, Boise LH, Lee KP, Nikiforov MA. KLF9 is a novel transcriptional regulator of bortezomib- and LBH589-induced apoptosis in multiple myeloma cells. Blood. 2012; 119:1450-1458
  • Mannava S, Moparthy KC, Wheeler LJ, Natarajan, V, Zucker SN, Fink EE, Im M, Flanagan S, Shewach DS, Burhans, WC, Mathews CK, Nikiforov MA. Depletion of deoxyribonucleotide pools is an endogenous source of DNA damage in cells undergoing oncogene-induced senescence. American Journal of Pathology; 2012; 182:142-151.
  • Mannava S, Omilian AR, Wawrzyniak JA, Fink EE, Zhuang D, Miecznikowski JC, Marshall JR, Soengas MS, Sears RC, Morrison CD, Nikiforov MA. PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells. Oncogene; 2012; 31:1484-1492