While cancer treatments have improved dramatically over the last several decades, many cancer types still defy standard treatments, including triple-negative breast cancer. In advance of a SynBioBeta 2020 session that will feature her work, I spoke with Dr. Karmella Haynes, an associate professor and biological engineer at the Winship Cancer Institute at Emory University, about her work in engineering chromatin proteins to develop novel therapies for this challenging disease.
Triple-negative breast cancer: what’s at stake?
Triple-negative breast cancer is an aggressive cancer subtype that disproportionately affects Black women.
Breast cancer is typically treated with hormone therapies. For such therapies to be effective, at least one of three receptor proteins must be present on the cancer cell’s surface. However, in triple-negative breast cancer, all three receptors have been either silenced or mutated, hence the ‘triple-negative’ designation.
Haynes says that triple-negative breast cancer cells have deactivated all three components that 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 chemo, but the fatality rate remains very high.
“Black women are 42% more likely to die of breast cancer, even though Black and white women have roughly the same rate of breast cancer diagnosis,” Haynes told me.
Genes aren’t just DNA: A novel 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 isn’t the whole story. Additional chemical compounds called epigenetic marks are attached to the DNA and affect gene expression significantly.
“A gene isn’t just DNA, biochemically speaking, and it’s naïve to pretend that it is.” Haynes thinks we need to give greater consideration to the proteins found around DNA when we think about what a gene is. When it comes to treating cancer, these epigenetic proteins play a significant role.
“It turns out that there are plenty 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’s responsible for coiling up the long double helix so that it doesn’t get tangled in the cell nucleus. But researchers have found that disruptions to chromatin and how it packages DNA can alter how genes themselves are expressed. For Haynes, cancer research has neglected chromatin for far too long. “If you continue to ignore how DNA is housed in a human cell, you’re not going to be able to do anything substantial in a million years,” she insists.
It’s now clear that chromatin does more than keep the genome organized. It can also control the ‘on/off’ switches that control whether a gene is expressed and the magnitude or intensity of gene expression.
“If we can turn those [tumor suppressor genes] back on, that could be an alternative to chemo,” says Haynes.
Creating a platform for chromatin engineering
Haynes’ lab is developing a screening platform to find natural and artificial proteins that bind with and modify specific chromatin. To streamline this process, Haynes and her team are using cell-free protein expression.
Biological researchers typically use bacteria to express proteins, but this is an extremely time-consuming process. Using cell-free protein expression, Haynes and her team can quickly produce 500 different proteins in the exact quantities they need. Speed and low product waste are especially important since most protein variants turn out to be ineffective. “We want to make failure cheap and fast because there are going to be a lot of molecular failures,” says Haynes.
Haynes is also screening chromatin mark reader proteins to find the most tightly binding gene activators. Ideally, these activators will bind to a silenced tumor-suppressing gene that has been turned ‘off’ and flip its switch. Once back ‘on’, the gene can get to work killing the cancer. The more strongly these activators can bind, the more effective the treatment will be.
Critical intersectionalities in research and healthcare
Beyond Haynes’ research, it’s important to address the intersectional struggles she has faced as a Black woman in STEM. “You definitely have to find ways to navigate this stuff to keep your career alive,” she says. Haynes’ experiences are not unique. Well-documented, pervasive racism (and sexism) deters people of color from majoring in or staying in STEM. Scientists of color, particularly Black women, regularly face covert and overt discrimination in their own fields.
And because her work straddles traditionally descriptive fields like biology with newer engineering approaches in synthetic biology, Haynes faces a different kind of discrimination from her fellow researchers. A peer reviewer once asserted that she was “not a real chromatin biologist.” Another peer told her that he didn’t think she was doing “real” synthetic biology.
For her part, Haynes has continued her chromatin research for triple-negative breast cancer, but the disparities this type of cancer causes for Black women are still on her mind. In the US, Black women often experience unequal access to healthcare, racial bias, and dismissive treatment from healthcare providers. A disease like triple-negative breast cancer can compound these inequities.
“My draw to triple-negative breast cancer is not only that it’s a tough problem but that it disproportionately affects African American women,” says Haynes. “Even if my protein doesn’t work, maybe I can contribute in some other way, in a surprising way. I think that would be pretty important.”
Therapeutics 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 unwelcome in their own fields of expertise. The scientific community must take significant, anti-racist steps to empower all of our most innovative minds to tackle humanity’s most pressing challenges. Only then can we truly succeed.
Subscribe to my weekly synthetic biology newsletter. Thank you to Fiona Rose Mischel for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta 2020 Global Synthetic Biology Summit.0