ABOUT THE RESEARCHER

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.

BACKGROUND

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

Publications powered by Harvard Catalyst Profiles

  1. Process development and safety evaluation of ABCB5+ limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency. Stem Cell Res Ther. 2021 Mar 19; 12(1):194. View abstract
  2. ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment. Stem Cells. 2021 Feb 20. View abstract
  3. Clinical Implications of Colorectal Cancer Stem Cells in the Age of Single-Cell Omics and Targeted Therapies. Gastroenterology. 2021 May; 160(6):1947-1960. View abstract
  4. Process data of allogeneic ex vivo-expanded ABCB5+ mesenchymal stromal cells for human use: off-the-shelf GMP-manufactured donor-independent ATMP. Stem Cell Res Ther. 2020 11 16; 11(1):482. View abstract
  5. Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data. Cytotherapy. 2021 Feb; 23(2):165-175. View abstract
  6. Targeting the ABC transporter ABCB5 sensitizes glioblastoma to temozolomide-induced apoptosis through a cell-cycle checkpoint regulation mechanism. J Biol Chem. 2020 05 29; 295(22):7774-7788. View abstract
  7. Loss of the Epigenetic Mark 5-hmC in Psoriasis: Implications for Epidermal Stem Cell Dysregulation. J Invest Dermatol. 2020 06; 140(6):1266-1275.e3. View abstract
  8. PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study. Oncologist. 2019 Dec 05. View abstract
  9. PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study. Oncologist. 2020 03; 25(3):e520-e527. View abstract
  10. Investigation of factors associated with ABCB5-positive limbal stem cell isolation yields from human donors. Ocul Surf. 2020 01; 18(1):114-120. View abstract
  11. Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist. Stem Cells. 2019 08; 37(8):1057-1074. View abstract
  12. In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials. Cytotherapy. 2019 05; 21(5):546-560. View abstract
  13. Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles. Cancers (Basel). 2019 Jan 30; 11(2). View abstract
  14. ATP-binding cassette member B5 (ABCB5) promotes tumor cell invasiveness in human colorectal cancer. J Biol Chem. 2018 07 13; 293(28):11166-11178. View abstract
  15. Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies. Expert Opin Biol Ther. 2018 05; 18(5):505-513. View abstract
  16. Limbal stem cells: identity, developmental origin, and therapeutic potential. Wiley Interdiscip Rev Dev Biol. 2018 03; 7(2). View abstract
  17. Rapid generation of Col7a1-/- mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells. Lab Invest. 2017 10; 97(10):1218-1224. View abstract
  18. Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device. Oncotarget. 2017 Jun 27. View abstract
  19. Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device. Oncotarget. 2017 Sep 15; 8(40):67355-67368. View abstract
  20. 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. View abstract
  21. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells. Stem Cells. 2016 09; 34(9):2393-406. View abstract
  22. ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth. J Invest Dermatol. 2016 Apr; 136(4):838-846. View abstract
  23. Effects of Malignant Melanoma Initiating Cells on T-Cell Activation. Methods Mol Biol. 2016 Jan 20. View abstract
  24. Isolation of Circulating Melanoma Cells. Methods Mol Biol. 2015 Sep 29. View abstract
  25. Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell. 2015 Sep 10; 162(6):1242-56. View abstract
  26. ABCB5 Identifies Immunoregulatory Dermal Cells. Cell Rep. 2015 Sep 08; 12(10):1564-74. View abstract
  27. Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment. J Invest Dermatol. 2015 Aug; 135(8):2040-2048. View abstract
  28. Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human Conjunctival Melanoma. Ocul Oncol Pathol. 2015 Apr; 1(3):182-189. View abstract
  29. Restoring the cornea from limbal stem cells. Regen Med. 2015; 10(1):1-4. View abstract
  30. Nestin depletion induces melanoma matrix metalloproteinases and invasion. Lab Invest. 2014 Dec; 94(12):1382-95. View abstract
  31. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014 Jul 17; 511(7509):353-7. View abstract
  32. ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit. Cancer Res. 2014 Aug 01; 74(15):4196-207. View abstract
  33. The multidrug-resistance transporter ABCB5 is expressed in human placenta. Int J Gynecol Pathol. 2014 Jan; 33(1):45-51. View abstract
  34. Stem cells and targeted approaches to melanoma cure. Mol Aspects Med. 2014 Oct; 39:33-49. View abstract
  35. Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk. Biochem Biophys Res Commun. 2013 Jul 05; 436(3):536-42. View abstract
  36. 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. View abstract
  37. Synergy of photoacoustic and fluorescence flow cytometry of circulating cells with negative and positive contrasts. J Biophotonics. 2013 May; 6(5):425-34. View abstract
  38. Metabolic inhibition of galectin-1-binding carbohydrates accentuates antitumor immunity. J Invest Dermatol. 2012 Feb; 132(2):410-20. View abstract
  39. ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients. Cancer Res. 2011 Aug 01; 71(15):5307-16. View abstract
  40. Colorectal Cancer Stem Cells: Biology and Therapeutic Implications. Curr Colorectal Cancer Rep. 2011 Jun; 7(2):128-135. View abstract
  41. The pro-apoptotic protein Bim is a microRNA target in kidney progenitors. J Am Soc Nephrol. 2011 Jun; 22(6):1053-63. View abstract
  42. SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study. Exp Dermatol. 2011 Apr; 20(4):339-45. View abstract
  43. VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth. Cancer Res. 2011 Feb 15; 71(4):1474-85. View abstract
  44. Isolation of tumorigenic circulating melanoma cells. Biochem Biophys Res Commun. 2010 Nov 26; 402(4):711-7. View abstract
  45. The in vitro spheroid melanoma cell culture assay: cues on tumor initiation? J Invest Dermatol. 2010 Jul; 130(7):1769-71. View abstract
  46. A novel in vivo regulatory role of P-glycoprotein in alloimmunity. Biochem Biophys Res Commun. 2010 Apr 09; 394(3):646-52. View abstract
  47. Tumor initiation in human malignant melanoma and potential cancer therapies. Anticancer Agents Med Chem. 2010 Feb; 10(2):131-6. View abstract
  48. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 2010 Jan 15; 70(2):697-708. View abstract
  49. The therapeutic promise of the cancer stem cell concept. J Clin Invest. 2010 Jan; 120(1):41-50. View abstract
  50. A gene encoding a multidrug-resistance human P-glycoprotein homologue on chromosome 7p15-2 and uses thereof. 2009. View abstract
  51. Identification and targeting of cancer stem cells. Bioessays. 2009 Oct; 31(10):1038-49. View abstract
  52. Antitumor immunity and cancer stem cells. Ann N Y Acad Sci. 2009 Sep; 1176:154-69. View abstract
  53. ABCB5 gene amplification in human leukemia cells. Leuk Res. 2009 Oct; 33(10):1303-5. View abstract
  54. 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. View abstract
  55. Tumour-Promoting Vasculogenic Channels of Cancer Stem Cell Origin. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 191. View abstract
  56. Inhibition of T cell activation by melanoma stem cells. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 191-192. View abstract
  57. Detection and Quantification of Circulating Melanoma Cells. 7th World Congress on Melanoma, May 12 -16 2009, Vienna, Austria. 2009; 123. View abstract
  58. 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). View abstract
  59. 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). View abstract
  60. Solid tumor stem cells – implications for cancer therapy. Regulatory Networks in Stem Cells. 2009. View abstract
  61. The effects of tamoxifen on immunity. Curr Med Chem. 2009; 16(24):3076-80. View abstract
  62. Solid tumor stem cells – implications for cancer therapy. Regulatory Networks in Stem Cells (V.K. Rajasekhar and M.C. Vemuri, Editors.). 2009; 527-543. View abstract
  63. Gene encoding a multidrug resistance human P-glycoprotein homologue on chromosome 7p15-21 and uses thereof. 2008. View abstract
  64. Gene encoding a multidrug-resistance human P-glycoprotein homologue on chromosome 7p15-2 and uses thereof. 2008. View abstract
  65. Therapeutic and diagnostic methods relating to cancer stem cells. 2008. View abstract
  66. Identification of cells initiating human melanomas. International Investigative Dermatology 2008 Meeting. 2008; Kyoto, Japan May 14-17 2008. View abstract
  67. Identification of cells initiating human melanomas. AACR Annual Meeting 2008. 2008; San Diego, CA, USA April 12-16. View abstract
  68. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 2008 Feb; 21(1):39-55. View abstract
  69. Identification of cells initiating human melanomas. Nature. 2008 Jan 17; 451(7176):345-9. View abstract
  70. ABCB5 positive mesenchymal stem cells as immunomodulators. 2007. View abstract
  71. Targeting ABCB5 for cancer therapy. 2007. View abstract
  72. P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation. Am J Transplant. 2006 Dec; 6(12):2884-93. View abstract
  73. Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. J Cell Biol. 2006 Oct 09; 175(1):99-110. View abstract
  74. 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. View abstract
  75. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005 May 15; 65(10):4320-33. View abstract
  76. A gene encoding a multidrug resistance human P-glycoprotein homologue on chromosome 7p15-21 and uses thereof. 2005. View abstract
  77. 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. View abstract
  78. Immunomodulatory functions of mesenchymal stem cells. Lancet. 2004 May 01; 363(9419):1411-2. View abstract
  79. 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. View abstract
  80. P-glycoprotein--a novel therapeutic target for immunomodulation in clinical transplantation and autoimmunity? Curr Drug Targets. 2003 Aug; 4(6):469-76. View abstract
  81. P-glycoprotein and alloimmune T-cell activation. Clin Appl Immunol Rev. 2003 Jul; 4(1):3-14. View abstract
  82. Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol. 2001 Feb 15; 166(4):2451-9. View abstract
  83. Monoclonal Antibody Targeting of Adhesion Molecules. Current and Future Immunosuppressive Therapies Following Transplantation. 2001; 249-263. View abstract
  84. Tolerance: is it time to move to the clinic?. Current and Future Immunosuppressive Therapies Following Transplantation. 2001; 293-313. View abstract
  85. 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. View abstract
  86. [Reversible esophageal dysfunction as a side effect of levodopa]. Bildgebung. 1996 Mar; 63(1):48-50. View abstract
  87. 31P-NMR-spektroskopische Studien zur Multidrug-Resistenz des menschlichen Nierenzellkarzinoms [Doctoral Dissertation]. 1995. View abstract