Ahmed M. Raafat Ph.D.
Staff Scientist

My research focuses on the role of ovarian hormones, growth factors and Notch genes in normal mammary development and breast cancer. The main objective of my research is to develop novel therapies to prevent and treat breast cancer.  This is done by identifying and dissecting pathways that are involved in tumor initiation, progression and metastasis.

Animal models and global gene expression methods are employed to detect and evaluate genes important in normal mammary and tumorigenic phenotypes.

Areas of Expertise
1) breast cancer, 2) normal mammary development, 3) animal models, 4) molecular biology, 5) cell biology

Contact Info

Ahmed M. Raafat Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 1118
Bethesda, MD 20892
301-496 2454
Ahmed.Raafat@nih.gov

Mechanism and consequences of Notch4/Int3 signaling on mammary gland development and tumorigenesis:  Overexpression of Notch4 intracellular domain (Int3)  in the WAP-Int3 or MMTV-Int3 mouse mammary gland results in tumor development in addition to the lack of alveolar development. Dissection of Notch4 signaling showed that the impairment of mammary development is Rbpj (Notch receptors main transcriptional regulator) dependent but mammary tumor development is Rbpj independent. Currently I am investigating (1) the Notch4/Rbpj-independent pathway accountable for tumor development, (2) the mechanism by which Notch4/Int3 blocks alveolar development, and (3) Notch signaling in the triple negative breast cancer. To facilitate these studies, I have developed a Notch4/Int3 inducible mouse model.

Role of ovarian hormones in normal mammary gland development and etiology of breast cancer:  Postnatal developmental events of the mouse mammary gland play a role in the study of breast cancer. Mouse mammary gland developmental events are under the control of the ovarian hormones estrogen and progesterone, in addition to a wide variety of protein hormones and local growth factors. Ovarian hormones have been implicated in breast cancer development in humans. To study the role of ovarian hormones in breast cancer, I have developed and characterized several mouse models. Currently I am investigating (1) the cross-talk between estrogen and Notch signaling and its role in mammary stem cell self-renewal, survival and differentiation, and (2) the role of Cripto and Rspo2 in normal mammary development and tumorigenesis.

Animal models: Mouse and human mammary glands are similar in development and function. Therefore, mouse models for mammary development and breast cancer have been widely used to study histopathology, tumor progression and molecular mechanisms involved in normal mammary development and cancer development. Comparisons of results obtained using these mouse models are done with little attention to the background of the strain(s) used to obtain the results. Therefore, I am conducting a broad study to compare the mammary glands of the most commonly used mouse strains in making the models (FVB and Balb/c). Global gene expression methods will be utilized to detect important genes to illustrate similarities and differences between these two strains.

  1. Park JP, Raafat A, Feltracco JA, Blanding WM, Booth BW
    Stem Cells Dev. 22(8): 1297-306, 2013. [ Journal Article ]
  2. Raafat A, Strizzi L, Lashin K, Ginsburg E, McCurdy D, Salomon D, Smith GH, Medina D, Callahan R
    PLoS ONE. 7: e43624, 2012. [ Journal Article ]
  3. Raafat A, Lawson S, Bargo S, Klauzinska M, Strizzi L, Goldhar AS, Buono K, Salomon D, Vonderhaar BK, Callahan R
    Oncogene. 28: 219-30, 2009. [ Journal Article ]
  4. Raafat A, Zoltan-Jones A, Strizzi L, Bargo S, Kimura K, Salomon D, Callahan R
    Oncogene. 26: 662-72, 2007. [ Journal Article ]
  5. Raafat AM, Li S, Bennett JM, Hofseth LJ, Haslam SZ
    J Cell Physiol. 187(1): 81-9, 2001. [ Journal Article ]

Dr.Dr. Raafat obtained his MSc. and Ph.D. degrees from Michigan State University. He was a postdoctoral fellow at the Department of Physiology at Michigan State University, and spent 5 years as a research fellow in the Mammary Biology and Tumorigenesis Laboratory at the National Cancer Institute. Currently he works as a staff scientist in the Oncogenetics Section at the Basic Research Laboratory, where he has been studying the roles of ovarian hormones and oncogenes (Notch4/Int3) on mammary development and etiology of breast cancer.

Research

Mechanism and consequences of Notch4/Int3 signaling on mammary gland development and tumorigenesis:  Overexpression of Notch4 intracellular domain (Int3)  in the WAP-Int3 or MMTV-Int3 mouse mammary gland results in tumor development in addition to the lack of alveolar development. Dissection of Notch4 signaling showed that the impairment of mammary development is Rbpj (Notch receptors main transcriptional regulator) dependent but mammary tumor development is Rbpj independent. Currently I am investigating (1) the Notch4/Rbpj-independent pathway accountable for tumor development, (2) the mechanism by which Notch4/Int3 blocks alveolar development, and (3) Notch signaling in the triple negative breast cancer. To facilitate these studies, I have developed a Notch4/Int3 inducible mouse model.

Role of ovarian hormones in normal mammary gland development and etiology of breast cancer:  Postnatal developmental events of the mouse mammary gland play a role in the study of breast cancer. Mouse mammary gland developmental events are under the control of the ovarian hormones estrogen and progesterone, in addition to a wide variety of protein hormones and local growth factors. Ovarian hormones have been implicated in breast cancer development in humans. To study the role of ovarian hormones in breast cancer, I have developed and characterized several mouse models. Currently I am investigating (1) the cross-talk between estrogen and Notch signaling and its role in mammary stem cell self-renewal, survival and differentiation, and (2) the role of Cripto and Rspo2 in normal mammary development and tumorigenesis.

Animal models: Mouse and human mammary glands are similar in development and function. Therefore, mouse models for mammary development and breast cancer have been widely used to study histopathology, tumor progression and molecular mechanisms involved in normal mammary development and cancer development. Comparisons of results obtained using these mouse models are done with little attention to the background of the strain(s) used to obtain the results. Therefore, I am conducting a broad study to compare the mammary glands of the most commonly used mouse strains in making the models (FVB and Balb/c). Global gene expression methods will be utilized to detect important genes to illustrate similarities and differences between these two strains.

Publications

  1. Park JP, Raafat A, Feltracco JA, Blanding WM, Booth BW
    Stem Cells Dev. 22(8): 1297-306, 2013. [ Journal Article ]
  2. Raafat A, Strizzi L, Lashin K, Ginsburg E, McCurdy D, Salomon D, Smith GH, Medina D, Callahan R
    PLoS ONE. 7: e43624, 2012. [ Journal Article ]
  3. Raafat A, Lawson S, Bargo S, Klauzinska M, Strizzi L, Goldhar AS, Buono K, Salomon D, Vonderhaar BK, Callahan R
    Oncogene. 28: 219-30, 2009. [ Journal Article ]
  4. Raafat A, Zoltan-Jones A, Strizzi L, Bargo S, Kimura K, Salomon D, Callahan R
    Oncogene. 26: 662-72, 2007. [ Journal Article ]
  5. Raafat AM, Li S, Bennett JM, Hofseth LJ, Haslam SZ
    J Cell Physiol. 187(1): 81-9, 2001. [ Journal Article ]

Biography

Dr.Dr. Raafat obtained his MSc. and Ph.D. degrees from Michigan State University. He was a postdoctoral fellow at the Department of Physiology at Michigan State University, and spent 5 years as a research fellow in the Mammary Biology and Tumorigenesis Laboratory at the National Cancer Institute. Currently he works as a staff scientist in the Oncogenetics Section at the Basic Research Laboratory, where he has been studying the roles of ovarian hormones and oncogenes (Notch4/Int3) on mammary development and etiology of breast cancer.