10-24-2019
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Meet A Researcher Series – Luke McCaffrey, PhD, and Christine Ambrosone, PhD
Interview with Luke McCaffrey
Q: How did you find out about the Komen Tissue Bank, and why did it interest you?
I first became aware of the Komen Tissue Bank when I applied for a Komen Career Catalyst Research Grant. In the application material, the Komen Tissue Bank was promoted and researchers were encouraged to consider using this resource. After we were awarded the Komen grant, we applied to the Komen Tissue Bank for access to tissue. The staff at the Komen Tissue Bank have been incredibly helpful to assist us with identifying suitable samples and providing them for our studies.
After we were awarded the Komen grant, we applied to the Komen Tissue Bank for access to tissue. The staff at the Komen Tissue Bank have been incredibly helpful to assist us with identifying suitable samples and providing them for our studies.
Q: What types of samples have you obtained from the Komen Tissue Bank?
We have obtained cryopreserved tissue from the Komen Tissue Bank. These tiny fragments of breast tissue contain many different types of normal cells, including one type called epithelial cells. Epithelial cells form the ducts and lobules within the breast, which breast cancers initially arise from. We isolate these epithelial cells from the tissue fragments and grow them in the lab in a specialized three-dimensional environment that allows them to form complex structures that mimics the normal breast structure. We then introduce cancer-causing alterations to the cells and observe how normal cells become cancer cells.
Q: What do you hope to discover/have you discovered in your research?
In addition to the growth of too many cells, breast cancers are characterized by loss of normal tissue structure. Before cancer forms, the structure of breast ducts becomes altered, which in some cases creates a permissive state for the further development of breast cancers. A goal of our research is to understand how this permissive environment is created and why some will develop into breast cancer, and others will not. Recent work from my lab has identified mechanisms by which normal breast tissue undergoes a step-wise progression to become cancer. We will use the tissue from the Komen Tissue Bank to understand what factors cause these early changes to the breast that are most likely to progress to cancer. We will also investigate how cells from women at a high-risk of developing breast cancer may be more susceptible to cancer than others. We also found that some early steps in the transition from normal to cancer may be reversible. We are interested to determine how to efficiently reverse these early steps and whether it could provide long-term protection from breast cancer.
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
Little known about the mechanisms underlying breast cancer initiation and early disease progression, and why some women develop breast cancer, and others do not. One of the major challenges has been access to normal breast tissue to understand how cancer initiates. The Komen Tissue Bank is the largest normal breast tissue bank worldwide and provides access to samples that represent a wide range of risk groups. This makes our studies possible by comparing the behavior of cells from high-risk and low-risk tissues. I am immensely appreciative of the Komen Tissue Bank staff and donors for making this important resource available to researchers.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
I believe that prevention is the next frontier for molecular breast cancer research. My hope is that our work will contribute to help improve risk assessment for women who are high-risk for breast cancer. By understanding the molecular mechanisms involved in breast cancer initiation, we hope to eventually develop unique and safe treatments to prevent breast cancer in high-risk women.
Q: Our readers would love to know some personal information about you. Do you have a non-science hobby? Have you traveled? Do you have a spouse and/or children? Have you ever been skydiving? Do you have any strange phobias? Did you plan to be an actor but became a researcher instead? Tell us anything at all that you feel comfortable talking about.
I am an outdoor enthusiast. In the winter, I enjoy snowshoeing in the wilderness. The rest of the year I enjoy bicycle touring and camping.
I first became aware of the Komen Tissue Bank when I applied for a Komen Career Catalyst Research Grant. In the application material, the Komen Tissue Bank was promoted and researchers were encouraged to consider using this resource. After we were awarded the Komen grant, we applied to the Komen Tissue Bank for access to tissue. The staff at the Komen Tissue Bank have been incredibly helpful to assist us with identifying suitable samples and providing them for our studies.
After we were awarded the Komen grant, we applied to the Komen Tissue Bank for access to tissue. The staff at the Komen Tissue Bank have been incredibly helpful to assist us with identifying suitable samples and providing them for our studies.
Q: What types of samples have you obtained from the Komen Tissue Bank?
We have obtained cryopreserved tissue from the Komen Tissue Bank. These tiny fragments of breast tissue contain many different types of normal cells, including one type called epithelial cells. Epithelial cells form the ducts and lobules within the breast, which breast cancers initially arise from. We isolate these epithelial cells from the tissue fragments and grow them in the lab in a specialized three-dimensional environment that allows them to form complex structures that mimics the normal breast structure. We then introduce cancer-causing alterations to the cells and observe how normal cells become cancer cells.
Q: What do you hope to discover/have you discovered in your research?
In addition to the growth of too many cells, breast cancers are characterized by loss of normal tissue structure. Before cancer forms, the structure of breast ducts becomes altered, which in some cases creates a permissive state for the further development of breast cancers. A goal of our research is to understand how this permissive environment is created and why some will develop into breast cancer, and others will not. Recent work from my lab has identified mechanisms by which normal breast tissue undergoes a step-wise progression to become cancer. We will use the tissue from the Komen Tissue Bank to understand what factors cause these early changes to the breast that are most likely to progress to cancer. We will also investigate how cells from women at a high-risk of developing breast cancer may be more susceptible to cancer than others. We also found that some early steps in the transition from normal to cancer may be reversible. We are interested to determine how to efficiently reverse these early steps and whether it could provide long-term protection from breast cancer.
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
Little known about the mechanisms underlying breast cancer initiation and early disease progression, and why some women develop breast cancer, and others do not. One of the major challenges has been access to normal breast tissue to understand how cancer initiates. The Komen Tissue Bank is the largest normal breast tissue bank worldwide and provides access to samples that represent a wide range of risk groups. This makes our studies possible by comparing the behavior of cells from high-risk and low-risk tissues. I am immensely appreciative of the Komen Tissue Bank staff and donors for making this important resource available to researchers.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
I believe that prevention is the next frontier for molecular breast cancer research. My hope is that our work will contribute to help improve risk assessment for women who are high-risk for breast cancer. By understanding the molecular mechanisms involved in breast cancer initiation, we hope to eventually develop unique and safe treatments to prevent breast cancer in high-risk women.
Q: Our readers would love to know some personal information about you. Do you have a non-science hobby? Have you traveled? Do you have a spouse and/or children? Have you ever been skydiving? Do you have any strange phobias? Did you plan to be an actor but became a researcher instead? Tell us anything at all that you feel comfortable talking about.
I am an outdoor enthusiast. In the winter, I enjoy snowshoeing in the wilderness. The rest of the year I enjoy bicycle touring and camping.
Interview with Christine Ambrosone
Q: How did you find out about the Komen Tissue Bank, and why did it interest you?
We have been doing research using tissues from breast tumors, particularly in relation to the effects of risk factors on changes in the breast. Clearly, tumor tissue does not represent the normal breast prior to cancer, but we were unaware of availability of normal breast tissue for use in research. A colleague of mine became aware of the Komen Tissue Bank through conversations with Dr. Ken Nephew. This seemed like the perfect resource for trying to understand how risk factors, particularly having children and not breastfeeding, may influence the etiology of more aggressive breast cancer (tumors that do not express the estrogen receptor [ER negative]).
Q: What types of samples have you obtained from the Komen Tissue Bank?
We obtained fresh frozen breast tissue from which we are extracting DNA and RNA, and also whole sections of fixed tissue to be able to stain for specific proteins. We requested samples from African-American women, with equal numbers of women who never had children, those who had children and breastfed, and those who gave birth but did not breastfeed.
Q: What do you hope to discover/have you discovered in your research?
Using tissue from breast tumors from African American women, we previously found that there were differences in changes in genes (DNA methylation) in tumors depending upon whether or not they were ER negative or ER positive. One of the most different genes was FOXA1, which appears to be involved in suppressing ER negative type cell precursors. We were surprised to see that these differences were greatest depending upon whether or not women had children. Because having children and not breastfeeding is associated with more aggressive ER negative breast cancer, we want to see if these reproductive factors result in changes to genes in the normal breast, which, with additional events, could results in either ER negative or ER positive breast cancer
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
The Komen Tissue Bank will allow us to address this key question, which we could only hypothesize about, but not test, with the breast cancer tissues that we had. We believe that it is a priceless, incredibly generous gift for women to consent to providing breast tissue, and are very grateful to be able to access these tissues to address our research questions.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
Our research is primarily aimed at cancer prevention. We are hoping that this research will help us understand how breast cancers arise, and what contributes to whether patients develop ER positive or ER negative breast cancer, which is more difficult to treat and has poorer prognosis. Understanding these causes can lead to prevention strategies. For example, findings may solidify the importance of breastfeeding to reduce the risk of ER- breast cancer, providing justification for developing educational programs aimed at populations at risk. A longer term goal of our study is to identify targets for chemoprevention that would mimic the protective effects of breast feeding.
Q: Our readers would love to know some personal information about you. Tell us anything at all that you feel comfortable talking about.
I returned to school fairly late in life and obtained my PhD when I was 45, after working in restaurants for a number of years and raising two children (it’s never too late!). I am now passionate about breast cancer research and really enjoy working – thinking, reading and writing to continue our work trying to understand the causes of breast cancer for prevention. Up until a couple of years ago, we lived on several acres outside of Buffalo, NY, had fruit trees, chickens and grew a large organic garden. I love cooking food that we have grown, and freezing and canning the rest. We have two grandsons who are growing up way too fast.
