Alan O. Perantoni, Ph.D.
Alan O. Perantoni, Ph.D.
Chief
Senior Investigator
Head, Differentiation and Neoplasia Section

Center for Cancer Research
National Cancer Institute

Building 538, Room 205B
Frederick, MD 21702-1201
301-846-6529

Dr. Perantoni has devoted his efforts to identifying (1) the ligands responsible for renal progenitor/stem cell survival and differentiation, (2) the molecular targets of those ligands, (3) the mechanisms responsible for the dysregulation of normal signaling in Wilms tumor, and (4) the targets of dysregulation in those tumors.

As Chief, he is responsible for a laboratory dedicated to the analysis of major developmental signaling pathways that contribute to cell growth, differentiation, morphogenesis, and cancer.

Areas of Expertise
1) kidney and reproductive tract development 2) renal progenitor signaling 3) STAT transcription factors in development and cancer 4) FGF and WNT signaling in kidney 5) Wilms tumor

Growth/Differentiation Factors in Organogenesis and Their Roles in Tumorigenesis

Morphogenesis in the differentiating metanephros is regulated by reciprocal interactions between ureteric bud (UB) epithelia and the metanephric mesenchyme (MM). The UB invades the overlying MM and induces conversion of the mesenchyme into stromal and epithelial elements, which form the nephron. In turn, the MM stimulates the UB to grow and branch, forming the collecting duct system. The Differentiation and Neoplasia Section focuses on the elucidation of mechanisms of inductive signaling in metanephric development, seeking (1) the ligands responsible for renal progenitor survival and nephronic differentiation, (2) other non-inductive regulatory factors of nephrogenesis, (3) the molecular targets of induction, (4) dysregulation of normal inductive signaling during development of pediatric neoplasms such as the Wilms tumor or congenital mesoblastic nephroma, and (5) targeting the dysregulated signaling in these tumors. The Section uses both explants of metanephric rudiments and mouse genetic models in these studies. We also have ongoing efforts to map the genetic locus responsible for sensitivity to nephroblastoma (Wilms) induction in rats. We expect that as we decipher the roles of various inductive signaling mechanisms in development and understand their dysregulation in tumorigenesis, our studies will lead to novel animal models and targeting agents for drug development.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Developmental Biology, Stem Cell Biology
Selected Key Publications
  1. Das A, Tanigawa S, Karner CM, Xin M, Lum L, Chen C, Olson EN, Perantoni AO, Carroll TJ.
    Nat. Cell Biol. 15: 1035-44, 2013. [ Journal Article ]
  2. Kitagaki J, Ueda Y, Chi X, Sharma N, Elder CM, Truffer E, Costantini F, Lewandoski M, Perantoni AO.
    Development. 138: 5369-78, 2011. [ Journal Article ]
  3. Tanigawa S, Wang H, Yang Y, Sharma N, Tarasova N, Ajima R, Yamaguchi TP, Rodriguez LG, Perantoni AO.
    Dev Biol. 352: 58-69, 2011. [ Journal Article ]
  4. Timofeeva OA, Plisov S, Evseev AA, Peng S, Jose-Kampfner M, Lovvorn HN, Dome JS, Perantoni AO.
    Oncogene. 25: 7555-64, 2006. [ Journal Article ]
  5. Perantoni AO, Timofeeva O, Naillat F, Richman C, Pajni-Underwood S, Wilson C, Vainio S, Dove LF, Lewandoski M.
    Development. 132: 3859-3871, 2005. [ Journal Article ]

Dr. Perantoni received his Ph.D. in cell biology from Catholic University in 1983, having conducted his thesis research at the NCI. After serving as an assistant professor in the Pathology Department, University of Colorado Medical School, he returned to the NCI in 1992.

Name Position
Luis Alvarez Guest Researcher
Kristen Felt Special Volunteer
Michael Hall Ph.D. Postdoctoral Fellow (CRTA)
George J. Klarmann Jr. Ph.D. Special Volunteer
John Lee Postbaccalaureate Fellow
Tommy Nhat Nguyen Summer Student
Nirmala D. Sharma Research Biologist
Kylie Beth Tomlin Summer Student
Kangsun Yun Ph.D. Research Fellow

Summary

Dr. Perantoni has devoted his efforts to identifying (1) the ligands responsible for renal progenitor/stem cell survival and differentiation, (2) the molecular targets of those ligands, (3) the mechanisms responsible for the dysregulation of normal signaling in Wilms tumor, and (4) the targets of dysregulation in those tumors.

As Chief, he is responsible for a laboratory dedicated to the analysis of major developmental signaling pathways that contribute to cell growth, differentiation, morphogenesis, and cancer.

Areas of Expertise
1) kidney and reproductive tract development 2) renal progenitor signaling 3) STAT transcription factors in development and cancer 4) FGF and WNT signaling in kidney 5) Wilms tumor

Research

Growth/Differentiation Factors in Organogenesis and Their Roles in Tumorigenesis

Morphogenesis in the differentiating metanephros is regulated by reciprocal interactions between ureteric bud (UB) epithelia and the metanephric mesenchyme (MM). The UB invades the overlying MM and induces conversion of the mesenchyme into stromal and epithelial elements, which form the nephron. In turn, the MM stimulates the UB to grow and branch, forming the collecting duct system. The Differentiation and Neoplasia Section focuses on the elucidation of mechanisms of inductive signaling in metanephric development, seeking (1) the ligands responsible for renal progenitor survival and nephronic differentiation, (2) other non-inductive regulatory factors of nephrogenesis, (3) the molecular targets of induction, (4) dysregulation of normal inductive signaling during development of pediatric neoplasms such as the Wilms tumor or congenital mesoblastic nephroma, and (5) targeting the dysregulated signaling in these tumors. The Section uses both explants of metanephric rudiments and mouse genetic models in these studies. We also have ongoing efforts to map the genetic locus responsible for sensitivity to nephroblastoma (Wilms) induction in rats. We expect that as we decipher the roles of various inductive signaling mechanisms in development and understand their dysregulation in tumorigenesis, our studies will lead to novel animal models and targeting agents for drug development.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Developmental Biology, Stem Cell Biology

Publications

Selected Key Publications
  1. Das A, Tanigawa S, Karner CM, Xin M, Lum L, Chen C, Olson EN, Perantoni AO, Carroll TJ.
    Nat. Cell Biol. 15: 1035-44, 2013. [ Journal Article ]
  2. Kitagaki J, Ueda Y, Chi X, Sharma N, Elder CM, Truffer E, Costantini F, Lewandoski M, Perantoni AO.
    Development. 138: 5369-78, 2011. [ Journal Article ]
  3. Tanigawa S, Wang H, Yang Y, Sharma N, Tarasova N, Ajima R, Yamaguchi TP, Rodriguez LG, Perantoni AO.
    Dev Biol. 352: 58-69, 2011. [ Journal Article ]
  4. Timofeeva OA, Plisov S, Evseev AA, Peng S, Jose-Kampfner M, Lovvorn HN, Dome JS, Perantoni AO.
    Oncogene. 25: 7555-64, 2006. [ Journal Article ]
  5. Perantoni AO, Timofeeva O, Naillat F, Richman C, Pajni-Underwood S, Wilson C, Vainio S, Dove LF, Lewandoski M.
    Development. 132: 3859-3871, 2005. [ Journal Article ]

Biography

Dr. Perantoni received his Ph.D. in cell biology from Catholic University in 1983, having conducted his thesis research at the NCI. After serving as an assistant professor in the Pathology Department, University of Colorado Medical School, he returned to the NCI in 1992.

Team

Name Position
Luis Alvarez Guest Researcher
Kristen Felt Special Volunteer
Michael Hall Ph.D. Postdoctoral Fellow (CRTA)
George J. Klarmann Jr. Ph.D. Special Volunteer
John Lee Postbaccalaureate Fellow
Tommy Nhat Nguyen Summer Student
Nirmala D. Sharma Research Biologist
Kylie Beth Tomlin Summer Student
Kangsun Yun Ph.D. Research Fellow