Linda  Wolff, Ph.D.
Linda Wolff, Ph.D.
Scientist Emeritus

Center for Cancer Research
National Cancer Institute

Building 37, Room 4124A
Bethesda, MD 20892
301-496-6763

Dr. Wolff is the head of the Leukemogenesis Section, Laboratory of Cellular Oncology. She obtained her Ph.D. from Ohio State University where she carried out research on the immunological and oncogenic aspects of the feline leukemia virus. When she first joined the NCI in 1981 in Edward Scolnick's Laboratory of Tumor Virus Genetics, she continued investigations in retroviral pathogenesis under the mentorship of Sandra Ruscetti. Her ongoing research focuses on transformation of hematopoietic cells of the myelomonocytic pathway. She is currently on the editorial board of the journal Apoptosis. She regularly organizes biennual meetings on 'Molecular Aspects of Myeloid Stem Cell Development and Leukemia' and has been co-organizer of meetings on Retrovirus Pathogenesis.

Areas of Expertise
feline leukemia virus

The focus of the research is on the development of murine acute myeloid leukemia (AML) models using retroviruses and on the role of specific oncogenes and tumor suppressors in leukemia.

INK4b Tumor Suppressor

The p15INK4b gene is member of a family of cyclin dependent kinase inhibitors that prevent G1/S transition at the restriction point involving the RB pathway. The gene is upregulated in response to cytokines that induce differentiation and/or growth arrest. Importantly, it plays a significant role in hematopoietic neoplasia, since it is inactivated by hypermethylation in more than 80% of acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The lab has developed murine models in which targeted deletion of the gene can accelerate retrovirus-induced myeloid leukemia. Mice deficient in p15Ink4b are also being used to study the role of the gene in development of the myeloid cell compartment and homeostasis. In additional studies we are investigating the mechanisms involved in the transcriptional repression of the p15Ink4b promoter in leukemia.

The c-Myb Oncogene

The c-myb is essential for the development of hematopoietic cells and plays a role in proliferation, anti-apoptosis and differentiation. We have discovered that the c-myb can be activated to transform myeloid cells either by overexpression at the transcriptional level or by protein truncation which removes sequences that are critical for phosphorylation-induced ubiquitinization and 26S-proteasome degradation. In other studies, we have identified important target genes that c-Myb, a transcription factor, regulates and that are involved in mediating its transforming function in cells. c-Myb directly transactivates c-myc, a critical component in control of proliferation, and Bcl-2, an inhibitior of programmed cell death. Recently the laboratory has shown that c-Myb also inhibits expression of the tumor suppressor and cdk inhibitor, p15INK4b.

Selected Publications
  1. Wolff L, Bies J.
    Blood Cells Mol. Dis.. 50: 227-31, 2013. [ Journal Article ]
  2. Humeniuk R, Rosu-Myles M, Fares J, Koller R, Bies J, Wolff L.
    Blood Cancer J. 3: e99, 2013. [ Journal Article ]
  3. Humeniuk R, Rosu-Myles M, Fares J, Koller R, Bies J, Wolff L.
    Blood Cancer J. 2: e99, 2013. [ Journal Article ]
  4. Nishibe R, Watanabe W, Ueda T, Yamasaki N, Koller R, Wolff L, Honda Z, Ohtsubo M, Honda H.
    FEBS Lett.. [Epub ahead of print], 2013. [ Journal Article ]
  5. Wolff L, Humeniuk R.
    Stem Cells. [Epub ahead of print], 2013. [ Journal Article ]

Dr. Wolff is the head of the Leukemogenesis Section, Laboratory of Cellular Oncology. She obtained her Ph.D. from Ohio State University where she carried out research on the immunological and oncogenic aspects of the feline leukemia virus. When she first joined the NCI in 1981 in Edward Scolnick's Laboratory of Tumor Virus Genetics, she continued investigations in retroviral pathogenesis under the mentorship of Sandra Ruscetti. Her ongoing research focuses on transformation of hematopoietic cells of the myelomonocytic pathway. She is currently on the editorial board of the journal Apoptosis. She regularly organizes biennual meetings on 'Molecular Aspects of Myeloid Stem Cell Development and Leukemia' and has been co-organizer of meetings on Retrovirus Pathogenesis.

Name Position
Juraj Bies Ph.D. Staff Scientist
Joanna Fares B.S. Predoctoral Fellow
Rita Humeniuk Ph.D. Postdoctoral Fellow (CRTA)
Richard Koller B.S. Research Biologist
Junfang Zhang Ph.D. Postdoctoral Fellow (Visiting)

Summary

Dr. Wolff is the head of the Leukemogenesis Section, Laboratory of Cellular Oncology. She obtained her Ph.D. from Ohio State University where she carried out research on the immunological and oncogenic aspects of the feline leukemia virus. When she first joined the NCI in 1981 in Edward Scolnick's Laboratory of Tumor Virus Genetics, she continued investigations in retroviral pathogenesis under the mentorship of Sandra Ruscetti. Her ongoing research focuses on transformation of hematopoietic cells of the myelomonocytic pathway. She is currently on the editorial board of the journal Apoptosis. She regularly organizes biennual meetings on 'Molecular Aspects of Myeloid Stem Cell Development and Leukemia' and has been co-organizer of meetings on Retrovirus Pathogenesis.

Areas of Expertise
feline leukemia virus

Research

The focus of the research is on the development of murine acute myeloid leukemia (AML) models using retroviruses and on the role of specific oncogenes and tumor suppressors in leukemia.

INK4b Tumor Suppressor

The p15INK4b gene is member of a family of cyclin dependent kinase inhibitors that prevent G1/S transition at the restriction point involving the RB pathway. The gene is upregulated in response to cytokines that induce differentiation and/or growth arrest. Importantly, it plays a significant role in hematopoietic neoplasia, since it is inactivated by hypermethylation in more than 80% of acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The lab has developed murine models in which targeted deletion of the gene can accelerate retrovirus-induced myeloid leukemia. Mice deficient in p15Ink4b are also being used to study the role of the gene in development of the myeloid cell compartment and homeostasis. In additional studies we are investigating the mechanisms involved in the transcriptional repression of the p15Ink4b promoter in leukemia.

The c-Myb Oncogene

The c-myb is essential for the development of hematopoietic cells and plays a role in proliferation, anti-apoptosis and differentiation. We have discovered that the c-myb can be activated to transform myeloid cells either by overexpression at the transcriptional level or by protein truncation which removes sequences that are critical for phosphorylation-induced ubiquitinization and 26S-proteasome degradation. In other studies, we have identified important target genes that c-Myb, a transcription factor, regulates and that are involved in mediating its transforming function in cells. c-Myb directly transactivates c-myc, a critical component in control of proliferation, and Bcl-2, an inhibitior of programmed cell death. Recently the laboratory has shown that c-Myb also inhibits expression of the tumor suppressor and cdk inhibitor, p15INK4b.

Publications

Selected Publications
  1. Wolff L, Bies J.
    Blood Cells Mol. Dis.. 50: 227-31, 2013. [ Journal Article ]
  2. Humeniuk R, Rosu-Myles M, Fares J, Koller R, Bies J, Wolff L.
    Blood Cancer J. 3: e99, 2013. [ Journal Article ]
  3. Humeniuk R, Rosu-Myles M, Fares J, Koller R, Bies J, Wolff L.
    Blood Cancer J. 2: e99, 2013. [ Journal Article ]
  4. Nishibe R, Watanabe W, Ueda T, Yamasaki N, Koller R, Wolff L, Honda Z, Ohtsubo M, Honda H.
    FEBS Lett.. [Epub ahead of print], 2013. [ Journal Article ]
  5. Wolff L, Humeniuk R.
    Stem Cells. [Epub ahead of print], 2013. [ Journal Article ]

Biography

Dr. Wolff is the head of the Leukemogenesis Section, Laboratory of Cellular Oncology. She obtained her Ph.D. from Ohio State University where she carried out research on the immunological and oncogenic aspects of the feline leukemia virus. When she first joined the NCI in 1981 in Edward Scolnick's Laboratory of Tumor Virus Genetics, she continued investigations in retroviral pathogenesis under the mentorship of Sandra Ruscetti. Her ongoing research focuses on transformation of hematopoietic cells of the myelomonocytic pathway. She is currently on the editorial board of the journal Apoptosis. She regularly organizes biennual meetings on 'Molecular Aspects of Myeloid Stem Cell Development and Leukemia' and has been co-organizer of meetings on Retrovirus Pathogenesis.

Team

Name Position
Juraj Bies Ph.D. Staff Scientist
Joanna Fares B.S. Predoctoral Fellow
Rita Humeniuk Ph.D. Postdoctoral Fellow (CRTA)
Richard Koller B.S. Research Biologist
Junfang Zhang Ph.D. Postdoctoral Fellow (Visiting)