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Research Overview

Dr. Frank's research laboratory is currently focused on dissecting the relationship of multipotent stem cells residing in diverse human tissues to genetic diseases and cancer, with a special emphasis on the relevant role of the ATP-binding cassette transporter and chemoresistance gene ABCB5.

 

Research Background

Dr. Frank received her medical degree at the Kiev Medical Institute, in Kiev, Ukraine, and continued her training at Boston Children's Hospital and the Albert Einstein College of Medicine. In addition to her research role, Frank directs the Genetics Clinic at the VA Boston Medical Center, where she attends to patients with hereditary cancer syndromes. She also serves as an Associate Physician in the Division of Genetics at Brigham and Women's Hospital and is a member of the Harvard Center for Neurofibromatosis and Allied Disorders.

 

Publications

  1. Anti-Inflammatory and Anti-(Lymph)angiogenic Properties of an ABCB5+ Limbal Mesenchymal Stem Cell Population. Int J Mol Sci. 2024 Sep 07; 25(17). View Abstract
  2. Processes and outcomes from a clinical genetics e-consultation service managed by a primary care physician champion. Genet Med Open. 2024; 2:101831. View Abstract
  3. Accelerated Aging and Microsatellite Instability in Recessive Dystrophic Epidermolysis Bullosa-Associated Cutaneous Squamous Cell Carcinoma. J Invest Dermatol. 2024 Jul; 144(7):1534-1543.e2. View Abstract
  4. Protocol for isolating human BCAM-positive corneal progenitor cells by flow cytometry and cell sorting. STAR Protoc. 2023 Sep 15; 4(3):102503. View Abstract
  5. Corrigendum to ABCB5+ mesenchymal stromal cells facilitate complete and durable wound closure in recessive dystrophic epidermolysis bullosa [Cytotherapy 25 (2023) 782-788/1562]. Cytotherapy. 2023 Sep; 25(9):1016. View Abstract
  6. ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation. Cells. 2023 06 27; 12(13). View Abstract
  7. ABCB5+ mesenchymal stromal cells facilitate complete and durable wound closure in recessive dystrophic epidermolysis bullosa. Cytotherapy. 2023 07; 25(7):782-788. View Abstract
  8. Epigenetic Regulation of Corneal Epithelial Differentiation by TET2. Int J Mol Sci. 2023 Feb 02; 24(3). View Abstract
  9. ATF-3 expression inhibits melanoma growth by downregulating ERK and AKT pathways. Lab Invest. 2021 May; 101(5):636-647. View Abstract
  10. Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine. Int J Mol Sci. 2022 Dec 21; 24(1). View Abstract
  11. Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium. Stem Cell Res. 2022 10; 64:102936. View Abstract
  12. Translational development of ABCB5+ dermal mesenchymal stem cells for therapeutic induction of angiogenesis in non-healing diabetic foot ulcers. Stem Cell Res Ther. 2022 09 05; 13(1):455. View Abstract
  13. Limbal BCAM expression identifies a proliferative progenitor population capable of holoclone formation and corneal differentiation. Cell Rep. 2022 08 09; 40(6):111166. View Abstract
  14. Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. JCI Insight. 2021 11 22; 6(22). View Abstract
  15. Angiogenin Released from ABCB5+ Stromal Precursors Improves Healing of Diabetic Wounds by Promoting Angiogenesis. J Invest Dermatol. 2022 06; 142(6):1725-1736.e10. View Abstract
  16. Allogeneic ABCB5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial. JID Innov. 2022 Jan; 2(1). View Abstract
  17. High expression of SARS-CoV2 viral entry-related proteins in human limbal stem cells. Ocul Surf. 2022 01; 23:197-200. View Abstract
  18. Human iPS cells engender corneal epithelial stem cells with holoclone-forming capabilities. iScience. 2021 Jun 25; 24(6):102688. View Abstract
  19. 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 03 19; 12(1):194. View Abstract
  20. ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment. Stem Cells. 2021 07; 39(7):897-903. View Abstract
  21. Clinical Implications of Colorectal Cancer Stem Cells in the Age of Single-Cell Omics and Targeted Therapies. Gastroenterology. 2021 05; 160(6):1947-1960. View Abstract
  22. ATF-3 expression inhibits melanoma growth by downregulating ERK and AKT pathways. Lab Invest. 2021 05; 101(5):636-647. View Abstract
  23. 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 02; 23(2):165-175. View Abstract
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis. Neurol Genet. 2019 Apr; 5(2):e312. View Abstract
  30. An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery. NPJ Genom Med. 2018; 3:21. View Abstract
  31. 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
  32. 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
  33. Limbal stem cells: identity, developmental origin, and therapeutic potential. Wiley Interdiscip Rev Dev Biol. 2018 03; 7(2). View Abstract
  34. 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
  35. Reply. J Allergy Clin Immunol. 2017 05; 139(5):1720-1721. View Abstract
  36. Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma. Mol Genet Metab. 2017 05; 121(1):9-15. View Abstract
  37. The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma. Oncogene. 2017 06 15; 36(24):3464-3476. View Abstract
  38. Clinical Significance of Disseminated Pluripotent Tumor Cell Signature Expression in the Bone Marrow from Patients with Colorectal Cancer. J Cancer Sci Ther. 2017; 9(10):669-674. View Abstract
  39. Deficiency of the immunostimulatory cytokine IL-21 promotes intestinal neoplasia via dysregulation of the Th1/Th17 axis. Oncoimmunology. 2017; 6(1):e1261776. View Abstract
  40. Dissecting a Case of Abdominal Pain. N Engl J Med. 2016 10 27; 375(17):e35. View Abstract
  41. In Vivo Development of Transplant Arteriosclerosis in Humanized Mice Reflects Alloantigen Recognition and Peripheral Treg Phenotype of Lung Transplant Recipients. Am J Transplant. 2016 11; 16(11):3150-3162. View Abstract
  42. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci U S A. 2016 08 02; 113(31):8759-64. View Abstract
  43. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells. Stem Cells. 2016 09; 34(9):2393-406. View Abstract
  44. Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages. Oncoimmunology. 2016 Aug; 5(8):e1189052. View Abstract
  45. An argument for early genomic sequencing in atypical cases: a WISP3 variant leads to diagnosis of progressive pseudorheumatoid arthropathy of childhood. Rheumatology (Oxford). 2016 Mar; 55(3):586-9. View Abstract
  46. ABCB5 Identifies Immunoregulatory Dermal Cells. Cell Rep. 2015 Sep 08; 12(10):1564-74. View Abstract
  47. Mosaic focal dermal hypoplasia caused by a novel somatic mutation in PORCN detected in affected skin. Br J Dermatol. 2015 Aug; 173(2):568-70. View Abstract
  48. 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
  49. Restoring the cornea from limbal stem cells. Regen Med. 2015; 10(1):1-4. View Abstract
  50. Strong and deep Atlantic meridional overturning circulation during the last glacial cycle. Nature. 2015 Jan 01; 517(7532):73-6. View Abstract
  51. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014 Jul 17; 511(7509):353-7. View Abstract
  52. ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit. Cancer Res. 2014 Aug 01; 74(15):4196-207. View Abstract
  53. The multidrug-resistance transporter ABCB5 is expressed in human placenta. Int J Gynecol Pathol. 2014 Jan; 33(1):45-51. View Abstract
  54. Novel double heterozygous mutations in MEFV and NLRP3 genes in a patient with familial Mediterranean fever. J Clin Rheumatol. 2013 Dec; 19(8):452-3. View Abstract
  55. Stem cells and targeted approaches to melanoma cure. Mol Aspects Med. 2014 Oct; 39:33-49. View Abstract
  56. Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk. Biochem Biophys Res Commun. 2013 Jul 05; 436(3):536-42. View Abstract
  57. ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients. Cancer Res. 2011 Aug 01; 71(15):5307-16. View Abstract
  58. Colorectal Cancer Stem Cells: Biology and Therapeutic Implications. Curr Colorectal Cancer Rep. 2011 Jun; 7(2):128-135. View Abstract
  59. VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth. Cancer Res. 2011 Feb 15; 71(4):1474-85. View Abstract
  60. Isolation of tumorigenic circulating melanoma cells. Biochem Biophys Res Commun. 2010 Nov 26; 402(4):711-7. View Abstract
  61. A novel in vivo regulatory role of P-glycoprotein in alloimmunity. Biochem Biophys Res Commun. 2010 Apr 09; 394(3):646-52. View Abstract
  62. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 2010 Jan 15; 70(2):697-708. View Abstract
  63. The therapeutic promise of the cancer stem cell concept. J Clin Invest. 2010 Jan; 120(1):41-50. View Abstract
  64. Identification and targeting of cancer stem cells. Bioessays. 2009 Oct; 31(10):1038-49. View Abstract
  65. ABCB5 gene amplification in human leukemia cells. Leuk Res. 2009 Oct; 33(10):1303-5. View Abstract
  66. Solid tumor stem cells – implications for cancer therapy. Regulatory Networks in Stem Cells. Ed. by V.K. Rajasekhar and M.C. Vemuri. 2009. View Abstract
  67. Identification of cells initiating human melanomas. Nature. 2008 Jan 17; 451(7176):345-9. View Abstract
  68. 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
  69. Myogenic potential of muscle side and main population cells after intravenous injection into sub-lethally irradiated mdx mice. J Histochem Cytochem. 2005 Jul; 53(7):861-73. View Abstract
  70. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005 May 15; 65(10):4320-33. View Abstract
  71. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. American Association for Cancer Research 96th Annual Meeting, April 16-20,. 2005. View Abstract
  72. Chapter 16: Congentinal, metabolic and neuromuscular disorders in Respiratory Genetics. Ed. By Silverman, Weiss & Shapiro. 2005. View Abstract
  73. Differential expression of ABCB5 multidrug resistance P-glycoprotein in human breast cancer cell lines. June 8-11, Abstract P66-7. 2005; 467. View Abstract
  74. ABCB5 P-glycoprotein is a molecular marker of the Hoechst 33342 side population phenotype among human fetal skeletal muscle cells. The FASEB Journal (oral presentation). 2004; 18(4):A183. View Abstract
  75. 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
  76. Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter. American Journal of Human Genetics. 2003; 73(5 Supplement):327. View Abstract
  77. Commitment, differentiation, and diversification of avian cardiac progenitor cells. Ann N Y Acad Sci. 1995; (752):1-8. View Abstract

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