Research

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Markus Frank, MD

Markus Frank
Research Center:
Transplant Research Program
Division
Nephrology Research
Hospital Title:
Research Associate
Academic Title:
Assistant Professor of Pediatrics, Harvard Medical School
Research Focus Area:
Human P-glycoproteinATP-binding Cassette (ABC) TransportersStem CellCancer Stem Cell Biology
Contact:
617-919-2993
Contact Via Email
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Research Overview

Stem Cell Therapeutics
Dr. Frank's laboratory research focuses on the physiological and pathological roles of the human P-glycoprotein family of ATP-binding cassette (ABC) transporters. His laboratory has cloned and characterized a novel human ATP-binding cassette (ABC) transporter, ABCB5, which marks mesenchymal stem cell (MSC) subpopulations in human and murine skin. Dr. Frank's work has demonstrated a unique regulatory role of ABCB5 in the newly recognized phenomenon of stem cell fusion, and in cell fusion-dependent growth and differentiation. The identification and characterization of ABCB5 P-glycoprotein as a marker of adult skin-associated stem cells has allowed Dr. Frank's laboratory to initiate studies regarding the differentiation plasticity and immunomodulatory capacity of this unique cell subset in vitro and in vivo. Thus, current and future research efforts of Dr. Frank's laboratory are geared towards using adult skin-derived ABCB5+ stem cells as a transplantable cell source for novel therapeutic applications in tissue engineering and regeneration, and for stem cell-based modulation of transplant allograft rejection and autoimmune disorders.

Cancer Stem Cell Multidrug Resistance
Dr. Frank's laboratory has also shown that ABCB5 serves as a multidrug resistance transporter in human malignant melanoma, confering resistance to chemotherapy in vitro. Subsequent work has shown that ABCB5 expression 1) marks melanoma cells of stem cell phenotype and function; 2) correlates with tumorigenic growth of melanoma cells in vivo; and 3) is more abundant in human malignant melanoma than in benign melanocytic nevi in human patients. In tandem with fundamental approaches to further establish ABCB5 as an identifier of melanoma stem cells and to characterize the functional roles of ABCB5 in physiological and cancer stem cells, Dr. Frank's laboratory explores the clinical relevance of ABCB5 as a biomarker of melanoma progression, prognosis, and outcome, and to investigate the therapeutic efficacy of ABCB5 targeting in preclinical animal models of human malignant melanoma.

About Markus Frank, MD

Dr. Frank is a 1989 magna cum laude graduate of Harvard University in the field of Biochemistry and a 1992 M.D. graduate of the University of Heidelberg School of Medicine in Germany. Between 1994 and 1997 Dr. Frank received his internal medicine residency training at the Albert Einstein College of Medicine in New York and from 1997-2001 his fellowship training in nephrology at Brigham and Women's Hospital, Children's Hospital and Massachusetts General Hospital, Harvard Medical School, in Boston. Following a year of clinical nephrology training, Dr. Frank entered transplantation immunology research training under the mentorships of Drs. Mohamed Sayegh and David Briscoe at the Brigham and Women's Hospital and Children's Hospital Boston. He currently serves as an Assistant Professor of Pediatrics in the Transplantation Research Center at Harvard Medical School, as an Associate Physician in the Brigham and Women's Hospital Renal Division, and as Staff Scientist in the Division of Nephrology at Children's Hospital Boston and the Department of Dermatology at Brigham and Women's Hospital.

Publications

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  1. Lutz NW, Banerjee P, Wilson BJ, Ma J, Cozzone PJ, Frank MH. Expression of Cell-Surface Marker ABCB5 Causes Characteristic Modifications of Glucose, Amino Acid and Phospholipid Metabolism in the G3361 Melanoma-Initiating Cell Line. PLoS One. 2016; 11(8):e0161803.
  2. Jiang D, Muschhammer J, Qi Y, Kügler A, de Vries JC, Saffarzadeh M, Sindrilaru A, Beken SV, Wlaschek M, Kluth MA, Ganss C, Frank NY, Frank MH, Preissner KT, Scharffetter-Kochanek K. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells. Stem Cells. 2016 Sep; 34(9):2393-406.
  3. Kleffel S, Lee N, Lezcano C, Wilson BJ, Sobolewski K, Saab KR, Mueller H, Zhan Q, Posch C, Elco CP, DoRosario A, Garcia SS, Thakuria M, Wang YE, Wang LC, Murphy GF, Frank MH, Schatton T. ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth. J Invest Dermatol. 2016 Apr; 136(4):838-46.
  4. Kleffel S, Posch C, Barthel SR, Mueller H, Schlapbach C, Guenova E, Elco CP, Lee N, Juneja VR, Zhan Q, Lian CG, Thomi R, Hoetzenecker W, Cozzio A, Dummer R, Mihm MC, Flaherty KT, Frank MH, Murphy GF, Sharpe AH, Kupper TS, Schatton T. Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell. 2015 Sep 10; 162(6):1242-56.
  5. Schatton T, Yang J, Kleffel S, Uehara M, Barthel SR, Schlapbach C, Zhan Q, Dudeney S, Mueller H, Lee N, de Vries JC, Meier B, Vander Beken S, Kluth MA, Ganss C, Sharpe AH, Waaga-Gasser AM, Sayegh MH, Abdi R, Scharffetter-Kochanek K, Murphy GF, Kupper TS, Frank NY, Frank MH. ABCB5 Identifies Immunoregulatory Dermal Cells. Cell Rep. 2015 Sep 8; 12(10):1564-74.
  6. Gray ES, Reid AL, Bowyer S, Calapre L, Siew K, Pearce R, Cowell L, Frank MH, Millward M, Ziman M. Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment. J Invest Dermatol. 2015 Aug; 135(8):2040-8.
  7. Frank MH, Frank NY. Restoring the cornea from limbal stem cells. Regen Med. 2015; 10(1):1-4.
  8. Lee CW, Zhan Q, Lezcano C, Frank MH, Huang J, Larson AR, Lin JY, Wan MT, Lin PI, Ma J, Kleffel S, Schatton T, Lian CG, Murphy GF. Nestin depletion induces melanoma matrix metalloproteinases and invasion. Lab Invest. 2014 Dec; 94(12):1382-95.
  9. Ksander BR, Kolovou PE, Wilson BJ, Saab KR, Guo Q, Ma J, McGuire SP, Gregory MS, Vincent WJ, Perez VL, Cruz-Guilloty F, Kao WW, Call MK, Tucker BA, Zhan Q, Murphy GF, Lathrop KL, Alt C, Mortensen LJ, Lin CP, Zieske JD, Frank MH, Frank NY. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014 Jul 17; 511(7509):353-7.
  10. Wilson BJ, Saab KR, Ma J, Schatton T, Pütz P, Zhan Q, Murphy GF, Gasser M, Waaga-Gasser AM, Frank NY, Frank MH. ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit. Cancer Res. 2014 Aug 1; 74(15):4196-207.
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  12. Volpicelli ER, Lezcano C, Zhan Q, Girouard SD, Kindelberger DW, Frank MH, Frank NY, Crum CP, Murphy GF. The multidrug-resistance transporter ABCB5 is expressed in human placenta. Int J Gynecol Pathol. 2014 Jan; 33(1):45-51.
  13. Murphy GF, Wilson BJ, Girouard SD, Frank NY, Frank MH. Stem cells and targeted approaches to melanoma cure. Mol Aspects Med. 2014 Oct; 39:33-49.
  14. Lin JY, Zhang M, Schatton T, Wilson BJ, Alloo A, Ma J, Qureshi AA, Frank NY, Han J, Frank MH. Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk. Biochem Biophys Res Commun. 2013 Jul 5; 436(3):536-42.
  15. Reid AL, Millward M, Pearce R, Lee M, Frank MH, Ireland A, Monshizadeh L, Rai T, Heenan P, Medic S, Kumarasinghe P, Ziman M. Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression. Br J Dermatol. 2013 Jan; 168(1):85-92.
  16. Nedosekin DA, Sarimollaoglu M, Galanzha EI, Sawant R, Torchilin VP, Verkhusha VV, Ma J, Frank MH, Biris AS, Zharov VP. Synergy of photoacoustic and fluorescence flow cytometry of circulating cells with negative and positive contrasts. J Biophotonics. 2013 May; 6(5):425-34.
  17. Cedeno-Laurent F, Opperman MJ, Barthel SR, Hays D, Schatton T, Zhan Q, He X, Matta KL, Supko JG, Frank MH, Murphy GF, Dimitroff CJ. Metabolic inhibition of galectin-1-binding carbohydrates accentuates antitumor immunity. J Invest Dermatol. 2012 Feb; 132(2):410-20.
  18. Wilson BJ, Schatton T, Zhan Q, Gasser M, Ma J, Saab KR, Schanche R, Waaga-Gasser AM, Gold JS, Huang Q, Murphy GF, Frank MH, Frank NY. ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients. Cancer Res. 2011 Aug 1; 71(15):5307-16.
  19. Wilson BJ, Schatton T, Frank MH, Frank NY. Colorectal Cancer Stem Cells: Biology and Therapeutic Implications. Curr Colorectal Cancer Rep. 2011 Jun; 7(2):128-135.
  20. Ho J, Pandey P, Schatton T, Sims-Lucas S, Khalid M, Frank MH, Hartwig S, Kreidberg JA. The pro-apoptotic protein Bim is a microRNA target in kidney progenitors. J Am Soc Nephrol. 2011 Jun; 22(6):1053-63.
  21. Laga AC, Zhan Q, Weishaupt C, Ma J, Frank MH, Murphy GF. SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study. Exp Dermatol. 2011 Apr; 20(4):339-45.
  22. Frank NY, Schatton T, Kim S, Zhan Q, Wilson BJ, Ma J, Saab KR, Osherov V, Widlund HR, Gasser M, Waaga-Gasser AM, Kupper TS, Murphy GF, Frank MH. VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth. Cancer Res. 2011 Feb 15; 71(4):1474-85.
  23. Ma J, Lin JY, Alloo A, Wilson BJ, Schatton T, Zhan Q, Murphy GF, Waaga-Gasser AM, Gasser M, Stephen Hodi F, Frank NY, Frank MH. Isolation of tumorigenic circulating melanoma cells. Biochem Biophys Res Commun. 2010 Nov 26; 402(4):711-7.
  24. Schatton T, Frank MH. The in vitro spheroid melanoma cell culture assay: cues on tumor initiation? J Invest Dermatol. 2010 Jul; 130(7):1769-71.
  25. Izawa A, Schatton T, Frank NY, Ueno T, Yamaura K, Pendse SS, Margaryan A, Grimm M, Gasser M, Waaga-Gasser AM, Sayegh MH, Frank MH. A novel in vivo regulatory role of P-glycoprotein in alloimmunity. Biochem Biophys Res Commun. 2010 Apr 9; 394(3):646-52.
  26. Ma J, Frank MH. Tumor initiation in human malignant melanoma and potential cancer therapies. Anticancer Agents Med Chem. 2010 Feb; 10(2):131-6.
  27. Schatton T, Schütte U, Frank NY, Zhan Q, Hoerning A, Robles SC, Zhou J, Hodi FS, Spagnoli GC, Murphy GF, Frank MH. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 2010 Jan 15; 70(2):697-708.
  28. Frank NY, Schatton T, Frank MH. The therapeutic promise of the cancer stem cell concept. J Clin Invest. 2010 Jan; 120(1):41-50.
  29. Frank MH, Sayegh MH. A gene encoding a multidrug-resistance human P-glycoprotein homologue on chromosome 7p15-2 and uses thereof. 2009.
  30. Schatton T, Frank NY, Frank MH. Identification and targeting of cancer stem cells. Bioessays. 2009 Oct; 31(10):1038-49.
  31. Schatton T, Frank MH. Antitumor immunity and cancer stem cells. Ann N Y Acad Sci. 2009 Sep; 1176:154-69.
  32. Frank NY, Frank MH. ABCB5 gene amplification in human leukemia cells. Leuk Res. 2009 Oct; 33(10):1303-5.
  33. Gasser M, Frank MH, Schatton T, Frank NY, Grimm MW, Fertinger J, Germer CT, Waaga-Gasser AM . Identifizierung tumorinitiierender Zellen im Pankreaskarzinom: Untersuchung zur Bedeutung des MDR-Gens ABCB5. 126. Kongress der Deutschen Gesellschaft für Chirurgie, 28.04. - 01.05.2009, München. 2009; DOI: 10.3205/09dgch095.
  34. Frank N, Schatton T, Kim S, Zhan Q, Hsu MY, Widlund H, Fuhlbrigge R, Kupper T, Murphy G, Frank M. Tumour-Promoting Vasculogenic Channels of Cancer Stem Cell Origin. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 191.
  35. Schatton T, Schütte U, Zhan Q, Hörning A, Murphy GF, Frank MH. Inhibition of T cell activation by melanoma stem cells. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 191-192.
  36. Ziman M, Millward M, Frank M, Pearce R, Medic S, Slattery R, Brown M, Lazic S, Lee M, Kumarasinghe P, Heenan P. Detection and Quantification of Circulating Melanoma Cells. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 123.
  37. Frank NY, Schatton T, Kim S, Zhan Q, Hsu MY, Widlund HR, Fuhlbrigge RC, Kupper TS, Murphy GF, Frank MH. Melanoma vasculogenesis driven by cancer stem cells. Proceedings of the American Association for Cancer Research 100th Annual Meeting 2009, Denver, Colorado. 2009; 50(April 2009):759 (Abstract #3131).
  38. Schatton T, Schütte U, Zhan Q, Hörning A, Murphy GF, Frank MH. Cancer stem cell-mediated immunomodulation in human malignant melanoma. Proceedings of the American Association for Cancer Research 100th Annual Meeting 2009, Denver, Colorado. 2009; 50(April 2009):765 (Abstract #3164).
  39. Schatton T, Frank NY, Frank MH. Solid tumor stem cells – implications for cancer therapy. Regulatory Networks in Stem Cells. 2009.
  40. Behjati S, Frank MH. The effects of tamoxifen on immunity. Curr Med Chem. 2009; 16(24):3076-80.
  41. Schatton T, Frank NY, Frank MH. Solid tumor stem cells – implications for cancer therapy. Regulatory Networks in Stem Cells (V.K. Rajasekhar and M.C. Vemuri, Editors.). 2009; 527-543.
  42. Frank MH, Sayegh MH. Gene encoding a multidrug resistance human P-glycoprotein homologue on chromosome 7p15-21 and uses thereof. 2008.
  43. Frank MH, Sayegh MH. Gene encoding a multidrug-resistance human P-glycoprotein homologue on chromosome 7p15-2 and uses thereof. 2008.
  44. Frank MH, Frank NY. Therapeutic and diagnostic methods relating to cancer stem cells. 2008.
  45. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. International Investigative Dermatology 2008 Meeting. 2008; Kyoto, Japan May 14-17 2008.
  46. Schatton S, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. AACR Annual Meeting 2008. 2008; San Diego, CA, USA April 12-16.
  47. Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 2008 Feb; 21(1):39-55.
  48. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH. Identification of cells initiating human melanomas. Nature. 2008 Jan 17; 451(7176):345-9.
  49. Frank MH. ABCB5 positive mesenchymal stem cells as immunomodulators. 2007.
  50. Frank MH, Frank NY, Sayegh MH. Targeting ABCB5 for cancer therapy. 2007.
  51. Pendse SS, Behjati S, Schatton T, Izawa A, Sayegh MH, Frank MH. P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Am J Transplant. 2006 Dec; 6(12):2884-93.
  52. Frank NY, Kho AT, Schatton T, Murphy GF, Molloy MJ, Zhan Q, Ramoni MF, Frank MH, Kohane IS, Gussoni E. Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. J Cell Biol. 2006 Oct 9; 175(1):99-110.
  53. Lutz NW, Franks SE, Frank MH, Pomer S, Hull WE. Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays. MAGMA. 2005 Jul; 18(3):144-61.
  54. Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005 May 15; 65(10):4320-33.
  55. Frank MH, Sayegh MH. A gene encoding a multidrug resistance human P-glycoprotein homologue on chromosome 7p15-21 and uses thereof. 2005.
  56. Lapchak PH, Melter M, Pal S, Flaxenburg JA, Geehan C, Frank MH, Mukhopadhyay D, Briscoe DM. CD40-induced transcriptional activation of vascular endothelial growth factor involves a 68-bp region of the promoter containing a CpG island. Am J Physiol Renal Physiol. 2004 Sep; 287(3):F512-20.
  57. Frank MH, Sayegh MH. Immunomodulatory functions of mesenchymal stem cells. Lancet. 2004 May 1; 363(9419):1411-2.
  58. Frank NY, Pendse SS, Lapchak PH, Margaryan A, Shlain D, Doeing C, Sayegh MH, Frank MH. Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter. J Biol Chem. 2003 Nov 21; 278(47):47156-65.
  59. Pendse S, Sayegh MH, Frank MH. P-glycoprotein--a novel therapeutic target for immunomodulation in clinical transplantation and autoimmunity? Curr Drug Targets. 2003 Aug; 4(6):469-76.
  60. Pendse SS, Briscoe DM, Frank MH. P-glycoprotein and alloimmune T-cell activation. Clin Appl Immunol Rev. 2003 Jul; 4(1):3-14.
  61. Frank MH, Denton MD, Alexander SI, Khoury SJ, Sayegh MH, Briscoe DM. Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol. 2001 Feb 15; 166(4):2451-9.
  62. Frank MH. Briscoe DM. Monoclonal Antibody Targeting of Adhesion Molecules. Current and Future Immunosuppressive Therapies Following Transplantation. 2001; 249-263.
  63. Frank MH, Sayegh MH. Tolerance: is it time to move to the clinic?. Current and Future Immunosuppressive Therapies Following Transplantation. 2001; 293-313.
  64. Frank MH, Pomer S. Interferon alpha2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype. J Cancer Res Clin Oncol. 1999; 125(2):117-20.
  65. Kellner H, Liegl U, Frank M, Zoller WG. [Reversible esophageal dysfunction as a side effect of levodopa]. Bildgebung. 1996 Mar; 63(1):48-50.
  66. Frank MH. 31P-NMR-spektroskopische Studien zur Multidrug-Resistenz des menschlichen Nierenzellkarzinoms [Doctoral Dissertation]. 1995.
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