TheoryLab

A physician-scientist and thought leader whose research has helped change the clinical care of leukemia patients, Kevin Shannon, MD, continues to shape the field.

In this conversation, Dr. Shannon takes us through the challenges and hopes of leukemia research and describes what has him most excited about the state of cancer research.

Kevin Shannon, MD, is Professor in the Department of Pediatrics at the University of California, San Francisco, where he holds the Roma and Marvin Auerback Distinguished Professorship of Molecular Oncology. For his seminal research accomplishments, Dr. Shannon was named an American Cancer Society Research Professor.

2:09 – What are leukemias?

4:37 – What people should know about the state of leukemia research: “Leukemia has been one of the diseases where we’ve been able to apply the principle of understanding the underlying molecular basis of the disease to developing better treatments, and then implementing those treatments in the clinic.”

7:13 – How he decides which mutations in the DNA are the most important to study

9:53 – The difference between a DNA mutation and chromosomal abnormality, the problems they cause, and how they can even occur together

16:06 – What it means to say something is “druggable.”

18:36 – How leukemias become resistant to treatment

21:48 – How do you treat a disease that’s constantly changing?

25:12 – How his research provides insight into some of the broader questions in cancer research, beyond leukemia

27:56 – What excites him most about the state of cancer research today

32:19 – The impact of American Cancer Society funding on his career

36:35 – The outsize value of Institutional Research Grants, small pilot awards that the American Cancer Society awards to organizations such as the University of California at San Francisco

39:25 – His thoughts on the partnership between the American Cancer Society and St. Baldrick’s Foundation “to raise $11 million to fund the most innovative biological and clinical laboratory studies that have the greatest potential to quickly deliver new and improved treatments for kids with cancer.” (http://pressroom.cancer.org/StBaldricks2019)

42:26 – A message for cancer patients and caregivers

Lipids are fat molecules normally found in the membranes that surround each cell in the body. They also play a critical role in cellular communication. Ray Blind, PhD, and his lab have been investigating how a particular lipid turns cancer genes on and off in glioblastoma. In this interview he talks about how this happens as well as the very exciting therapeutic potential of his work.

Ray Blind, PhD, is Assistant Professor of Medicine at Vanderbilt University Medical Center.

2:57 – Lipids? What are lipids? Why are they important?

9:40 – What does the cutting edge of science tell us what it’s like in the nucleus?

15:28 – A nuclear lipid the Blind Lab studies interacts with chromatin. Why is that interaction important?

18:24 – How this nuclear lipid might be especially important in glioblastoma

21:39 – “You know the lipid is there, you know it has a role in cancer, we also assume that it has a role in normal cell development—is there a way to block it and not impact normal development or function? What would be the therapeutic translation?”

23:58 – “Well, this is what we’re really most excited about…” – chemical genetics, and the therapeutic potential of ongoing work in his lab

30:29 – The impact of ACS funding on his lab and on the direction of his research

34:01 – A message he’d like to share with cancer patients

Lipids are fat molecules normally found in the membranes that surround each cell in the body. They also play a critical role in cellular communication. Ray Blind, PhD, and his lab have been investigating how a particular lipid turns cancer genes on and off in glioblastoma. In this interview he talks about how this happens as well as the very exciting therapeutic potential of his work.

Ray Blind, PhD, is Assistant Professor of Medicine at Vanderbilt University Medical Center.

2:57 – Lipids? What are lipids? Why are they important?

9:40 – What does the cutting edge of science tell us what it’s like in the nucleus?

15:28 – A nuclear lipid the Blind Lab studies interacts with chromatin. Why is that interaction important?

18:24 – How this nuclear lipid might be especially important in glioblastoma

21:39 – “You know the lipid is there, you know it has a role in cancer, we also assume that it has a role in normal cell development—is there a way to block it and not impact normal development or function? What would be the therapeutic translation?”

23:58 – “Well, this is what we’re really most excited about…” – chemical genetics, and the therapeutic potential of ongoing work in his lab

30:29 – The impact of ACS funding on his lab and on the direction of his research

34:01 – A message he’d like to share with cancer patients

The circadian clock is an internal, 24-hour timekeeping system that’s synchronized with the light-dark cycle, and it’s resident in basically all our cells.

Kristin Eckel-Mahan, PhD, recently discovered an important molecular mechanism linking the circadian clock to hepatocellular carcinoma (HCC) growth. When her lab “repaired” the broken circadian clock within HCC cells, they were able to cause cell death. Her findings suggest that altering circadian function could provide prevention strategies and even, in the long term, treatment strategies for HCC, which is the most common type of primary liver cancer.

Kristin Eckel-Mahan, PhD, is Assistant Professor at the Center for Metabolic and Degenerative Diseases at the University of Texas Health Science Center at Houston.

2:15 – On the rise in incidence and mortality rates of hepatocellular carcinoma (HCC), the most common type of primary liver cancer

4:03 – Risk factors for HCC

5:24 – The role of fatty liver in increased HCC risk

9:22 – A particularly interesting description of the circadian clock and its importance in health

13:05 – The role of the circadian clock in liver cancer, and how she’s studying a protein’s role in circadian repression

20:34 – Therapeutic prospects related to altering the circadian system and the promise of chronotherapy (treatment of an illness or disorder that takes into account the body's natural rhythms and cycles)

27:52 – A message she’d like to share with cancer patients and caregivers

The circadian clock is an internal, 24-hour timekeeping system that’s synchronized with the light-dark cycle, and it’s resident in basically all our cells.

Kristin Eckel-Mahan, PhD, recently discovered an important molecular mechanism linking the circadian clock to hepatocellular carcinoma (HCC) growth. When her lab “repaired” the broken circadian clock within HCC cells, they were able to cause cell death. Her findings suggest that altering circadian function could provide prevention strategies and even, in the long term, treatment strategies for HCC, which is the most common type of primary liver cancer.

Kristin Eckel-Mahan, PhD, is Assistant Professor at the Center for Metabolic and Degenerative Diseases at the University of Texas Health Science Center at Houston.

2:15 – On the rise in incidence and mortality rates of hepatocellular carcinoma (HCC), the most common type of primary liver cancer

4:03 – Risk factors for HCC

5:24 – The role of fatty liver in increased HCC risk

9:22 – A particularly interesting description of the circadian clock and its importance in health

13:05 – The role of the circadian clock in liver cancer, and how she’s studying a protein’s role in circadian repression

20:34 – Therapeutic prospects related to altering the circadian system and the promise of chronotherapy (treatment of an illness or disorder that takes into account the body's natural rhythms and cycles)

27:52 – A message she’d like to share with cancer patients and caregivers

Around a quarter of people who smoke are non-daily smokers (those that smoke on some but not all days), and that number is increasing. The cancer risk of non-daily smoking is significant and existing treatments tend not to be tailored to this population.

To address this issue, Bettina Hoeppner, PhD, an experimental psychologist and Associate Professor of Psychology at Harvard Medical School and Massachusetts General Hospital, has developed a smartphone app, “Smiling Instead of Smoking,” to support non-daily smokers in quitting smoking. It serves “as a behavioral, in-the-pocket coach and uses positive psychology exercises to enhance quitting success.”

4:00 – What are “non-daily smokers?” Why is this a thing?

5:40 – Health risks of non-daily smoking

6:51 – Populations that are more at risk, and why they may be more likely to be non-daily smokers

9:31 – Barriers to quitting that are unique to non-daily smokers

12:05 – Why she uses a smart phone app in her research to help non-daily smokers quit smoking

14:28 – How her “Smiling Instead of Smoking” app works

18:07 – Why she chose happiness as an approach; how positive psychology is a promising new approach to smoking cessation

22:03 – On positive early returns her team has seen from the app—confidence in quitting increased, urge to smoke decreased, and perceptions of smoking became less positive

25:40 – On the potential to reach vulnerable populations with this app

28:13 – The impact American Cancer Society funding had on her career, taking a chance on funding work that was perceived as high risk

30:03 – A message she’d like to share with cancer survivors and caregivers

Around a quarter of people who smoke are non-daily smokers (those that smoke on some but not all days), and that number is increasing. The cancer risk of non-daily smoking is significant and existing treatments tend not to be tailored to this population.

To address this issue, Bettina Hoeppner, PhD, an experimental psychologist and Associate Professor of Psychology at Harvard Medical School and Massachusetts General Hospital, has developed a smartphone app, “Smiling Instead of Smoking,” to support non-daily smokers in quitting smoking. It serves “as a behavioral, in-the-pocket coach and uses positive psychology exercises to enhance quitting success.”

4:00 – What are “non-daily smokers?” Why is this a thing?

5:40 – Health risks of non-daily smoking

6:51 – Populations that are more at risk, and why they may be more likely to be non-daily smokers

9:31 – Barriers to quitting that are unique to non-daily smokers

12:05 – Why she uses a smart phone app in her research to help non-daily smokers quit smoking

14:28 – How her “Smiling Instead of Smoking” app works

18:07 – Why she chose happiness as an approach; how positive psychology is a promising new approach to smoking cessation

22:03 – On positive early returns her team has seen from the app—confidence in quitting increased, urge to smoke decreased, and perceptions of smoking became less positive

25:40 – On the potential to reach vulnerable populations with this app

28:13 – The impact American Cancer Society funding had on her career, taking a chance on funding work that was perceived as high risk

30:03 – A message she’d like to share with cancer survivors and caregivers

Cancer drugs that target “the machinery required for cell division” have been used successfully in clinics for decades. But these drugs have limitations. Many patients develop resistance and the side effects can be severe, because these drugs—in addition to targeting rapidly dividing tumor cells—also kill healthy cells.

Dr. Holland’s lab is searching for vulnerabilities in cell division that are unique to cancer cells. And he is building on some of his findings to develop a novel anti-cancer strategy that allows for the specific killing of proliferating tumor cells without affecting healthy dividing cells.

Andrew Holland, PhD, is Associate Professor in the Department of Molecular Biology and Genetics and the Department of Oncology at Johns Hopkins Hospital. He’s also a two-time American Cancer Society grantee. He recently received a Mission Boost Grant, which are designed to support select current and past ACS grantees specifically for the translation of their research to human testing.

2:23 – On what it was like to get the good news about his new Mission Boost Grant and the importance of funding translational research

5:47 – A helpful description of cell division and how it goes wrong in cancer

7:44 – Why drugs that target cell division are effective but have notable limitations

11:06 – A vulnerability around cell division his lab found in a specific type of breast cancer cell in cancer cells and normal cells that could be targeted

13:15 – How his lab’s work could lead to more targeted treatments and reduced side effects for breast cancer patients…

15:05 – …and potentially in other cancer types as well.

16:03 – On the hope that this could be scratching the surface of therapies that target vulnerabilities in the cell division of cancer cells

23:46 – A message for those whose lives have been impacted by cancer.

Cancer drugs that target “the machinery required for cell division” have been used successfully in clinics for decades. But these drugs have limitations. Many patients develop resistance and the side effects can be severe, because these drugs—in addition to targeting rapidly dividing tumor cells—also kill healthy cells.

Dr. Holland’s lab is searching for vulnerabilities in cell division that are unique to cancer cells. And he is building on some of his findings to develop a novel anti-cancer strategy that allows for the specific killing of proliferating tumor cells without affecting healthy dividing cells.

Andrew Holland, PhD, is Associate Professor in the Department of Molecular Biology and Genetics and the Department of Oncology at Johns Hopkins Hospital. He’s also a two-time American Cancer Society grantee. He recently received a Mission Boost Grant, which are designed to support select current and past ACS grantees specifically for the translation of their research to human testing.

2:23 – On what it was like to get the good news about his new Mission Boost Grant and the importance of funding translational research

5:47 – A helpful description of cell division and how it goes wrong in cancer

7:44 – Why drugs that target cell division are effective but have notable limitations

11:06 – A vulnerability around cell division his lab found in a specific type of breast cancer cell in cancer cells and normal cells that could be targeted

13:15 – How his lab’s work could lead to more targeted treatments and reduced side effects for breast cancer patients…

15:05 – …and potentially in other cancer types as well.

16:03 – On the hope that this could be scratching the surface of therapies that target vulnerabilities in the cell division of cancer cells

23:46 – A message for those whose lives have been impacted by cancer.

Cancer cells, explains Dorothy Sipkins, MD, PhD, “have this tendency to steal from or copy the way that normal cells respond to their microenvironment.”

In this conversation Dr. Sipkins explains how cancer cells profit from the tissue microenvironment. She also describes an important discovery made by her lab, showing how acute lymphoblastic leukemia (ALL) cells get around the blood-brain barrier to find the microenvironment in the central nervous system where they flourish.

Dorothy Sipkins, MD, PhD, is an associate professor at the Duke University Medical Center in the Division of Hematological Malignancies and Cellular Therapy. Dr. Sipkins runs a lab that’s focused on tissue microenvironments, or “niches, that regulate the migration, survival and regeneration of cancerous cells.”

3:42 – Why the tissue microenvironment is so important…

8:02 – …and how different microenvironments are crucial for cancer cells

11:55 –The treatment challenges resulting from the movement of acute lymphoblastic leukemia (ALL) cells into the central nervous system

16:17 – The long, difficult (but absolutely critical) journey her lab took to understanding how ALL gets around the blood-brain barrier to find the tissue microenvironment that allows it to flourish

30:36 – How her lab is trying to find “the best drug, the best tool, the best way to inhibit this process” in patients

31:07 – How ACS helped advance her research

32:52 – A message she’d like to share with survivors and caregivers