While cancer treatments have improved dramatically over the past few decades, many types of cancer still challenge standard treatments, including triple negative breast cancer. Upstream of a SynBioBeta 2020 session which will feature his work, I spoke with Dr Karmella Haynes, Associate Professor and Biological Engineer at the Winship Cancer Institute at Emory University, about his work in engineering chromatin proteins to develop new therapies for this difficult disease.
Triple negative breast cancer: what are the stakes?
Triple negative breast cancer is an aggressive cancer subtype that disproportionately affects black women.
Breast cancer is usually treated with hormonal therapy. For such therapies to be effective, at least one of the three receptor proteins must be present on the surface of the cancer cell. However, in triple negative breast cancer, all three receptors were either silenced or mutated, hence the designation “triple negative”.
Haynes says triple-negative breast cancer cells have turned off the three components the cell needs to respond to hormone therapy. As a result, this cancer tends to come back even after treatment. Other treatments are available for triple negative breast cancer, including surgery and chemotherapy, but the death rate remains very high.
“Black women are 42% more likely to die from breast cancer, even though black and white women have about the same rate of breast cancer diagnosis,” Haynes told me.
Genes are not just DNA: a new therapeutic approach
Haynes’ research targets triple negative breast cancer through the lens of gene activity and expression, a field called epigenetics. Genes are often understood as static segments of the classic double-stranded DNA helix, but that’s not all. Additional chemical compounds called epigenetic marks are attached to DNA and dramatically affect gene expression.
“A gene is not just DNA, biochemically speaking, and it is naive to claim that it is.” Haynes thinks we need to pay more attention to the proteins around DNA when we think about what a gene is. When it comes to treating cancer, these epigenetic proteins play an important role.
“It turns out that there are a lot of good tumor suppressor genes in some of these really hard-to-treat cancers,” says Haynes. However, these genes have been silenced by repressive chromatin.
Chromatin is an epigenetic protein that acts as a “packager” of DNA. It is responsible for coiling the long double helix so that it does not get tangled in the cell nucleus. But researchers have found that disruptions in chromatin and the way it conditions DNA can alter the way the genes themselves are expressed. For Haynes, cancer research has neglected chromatin for too long. “If you continue to ignore how DNA is housed in a human cell, you won’t be able to do anything substantial in a million years,” she insists.
It is now clear that chromatin does more than keep the genome organized. It can also control “on / off” switches that control whether a gene is expressed and the extent or intensity of gene expression.
“If we can transform these [tumor suppressor genes] back, this could be an alternative to chemo, ”says Haynes.
Creation of a platform for chromatin engineering
Haynes’ lab is developing a screening platform to find natural and artificial proteins that bind to and modify specific chromatin. To streamline this process, Haynes and his team are using protein expression without cells.
Biological researchers typically use bacteria to express proteins, but this is an extremely long process. Using cell-free protein expression, Haynes and his team can quickly produce 500 different proteins in the exact amounts they need. Speed and low product waste are especially important because most protein variants are found to be ineffective. “We want chess to be cheap and quick, because there is going to be a lot of molecular chess,” says Haynes.
Haynes also examines chromatin mark reading proteins to find the most closely related gene activators. Ideally, these activators will bind to a silent tumor suppressor gene that has been turned off and flip its switch. Once reactivated, the gene can go to work killing the cancer. The more strongly these activators can bind, the more effective the treatment will be.
Critical Intersectionalities in Research and Health Care
Beyond Haynes’ research, it’s important to address the intersectional struggles she has faced as a black woman in STEM. “You absolutely have to find ways to navigate this field to keep your career alive,” she says. Haynes’ experiences are not unique. Well documented, pervasive racism (and sexism) deters people of color from specializing or staying in STEM. Scientists of color, especially black women, face regularly hidden and open discrimination in their own areas.
And because his work overlaps traditionally descriptive fields like biology with new engineering approaches in synthetic biology, Haynes faces a different kind of discrimination than his fellow researchers. An examiner once claimed that she was “not a true chromatin biologist”. Another peer told her that he didn’t think she was doing “real” synthetic biology.
For her part, Haynes continued his chromatin research for triple negative breast cancer, but the disparities that this type of cancer causes in black women still concerns him. In the United States, black women often experience unequal access to health care, racial prejudice and dismissive treatment health care providers. A disease like triple negative breast cancer can make these inequalities worse.
“My appeal to triple negative breast cancer is not only that it is a difficult problem, but that it disproportionately affects African American women,” says Haynes. “Even though my protein isn’t working, maybe I can help in another way, in a surprising way. I think it would be quite important.
Therapeutic research needs more scientists like Haynes who are dedicated to finding answers for medically underserved populations, but we will never achieve our goals or ideals if scientists of color are not welcome in their own fields. of expertise. The scientific community must take significant anti-racist action to enable all of our most innovative minds to address humanity’s most pressing challenges. Only then can we really be successful.
Subscribe to my weekly synthetic biology newsletter. Thanks to Fiona Rose Mischel for additional research and reporting in this article. I am the founder of SynBioBeta, and some of the companies I write about are sponsors of the SynBioBeta Synthetic Biology Global Summit 2020.