The CDI Experts: Makohon-Moore Dissects Cancer’s Evolution

The bioreactor in the Makohon-Moore Lab looks, to a layman, like something out of an old science-fiction movie. The tubes and containers have minutely different environments - complete nutrition, deprivation, or starvation - to show how certain cancer cell lines within react and grow, survive or die, based on their surroundings. The fluids and material flow in and out, like it is in and of itself a living thing.

To a scientist like Alvin Makohon-Moore, this is the closest science has yet come to growing cancer in a controlled environment - mimicking its natural progression as closely as possible, in order to understand its dynamics… and how we may yet conquer it someday.

Makohon-Moore, assistant member of the Hackensack Meridian Center for Discovery and Innovation (CDI), arrived last year and has since been pushing forward the study of cancer’s evolution - how it arises, changes, grows, spreads, and ultimately, kills.

What has been dubbed “the emperor of all maladies” has been with humanity since we arose as a species - and Makohon-Moore reflects that scientists are still playing catch-up. To him, his bioreactor is going to shed some light in untangling cancer’s evolution, as entangled and entwined as it is with our shared history.

“This takes the evolutionary process and shows its dynamics in real time,” said Makohon-Moore recently in his laboratory.

Makohon-Moore is assessing the evolutionary foundations of cancer is producing results which complement so much of the CDI’s groundbreaking research in cancer. The work could help us better understand the timing and weaknesses of cancers, thereby pointing the way toward treatments in the years to come.

“Alvin is looking into the fundamentals of cancer evolution - which has the potential to better understand ways to change a cell’s cancer potential,” said David Perlin, Ph.D., the chief scientific officer and executive vice president of the CDI. “It complements so much of the other innovative cancer research going on at the CDI and at HMH; his findings are certain to advance the science of cancer significantly.”

DISCOVERING SCIENCE

Makohon-Moore grew up in Michigan. Early childhood was in a suburb of Detroit, with a father working as an attorney and a mother who was an art teacher, and one sister. As a teenager, his mother passed away from cancer, and the entire family moved to the state’s Upper Peninsula, to live near extended family on his father’s side.

He was a standout student, and a school-record-setter for the half mile on the high-school track team. He always figured he would be an English teacher, due to his love of reading and stories. But as an undergraduate, an introductory course on evolutionary science completely re-directed him; a 60-minute grainy video documentary  with Stephen Jay Gould (This View of Life, 1984) in class showed him that there was real room to tell stories - and to shape them - by looking at science. And he was hooked.

After a zoology degree at Michigan State University, he did his doctoral work in pathobiology at Johns Hopkins. There he came under the tutelage of a mentor, Christine Iacobuzio-Donahue, M.D., Ph.D., a physician-scientist who focuses on direct evolutionary mechanisms in pancreatic cancer. As a trained pathologist, Iacobuzio-Donahue has her students come into the morgue to observe and even participate in an  autopsy, to see the ravages of the disease they were studying, beyond just a small tissue sample. One was all that was required; Makohon-Moore ultimately took part in more than 100.

“From the autopsy, directly to the data, there’s just no substitute, for being hands-on, and seeing the reality of what we’re up against,’ said Makohon-Moore.

When Iacobuzio-Moore moved her laboratory from Johns Hopkins to Memorial Sloan Kettering in New York, Makohon-Moore finished out his degree, and his thesis: “The Genetic Evolution and Natural History of Pancreatic Adenocarcinoma.” Once completed, he re-joined his mentor at MSK to continue their work, especially on pancreatic cancer.

AN EVOLUTION

The focus on pancreatic cancer is apt: it’s an aggressive cancer which is among the deadliest right now, because it is often diagnosed too late for effective treatment. Makohon-Moore, in working with Iacobuzio-Donahue, made breakthroughs in understanding what makes this tumor type “tick.” Perhaps most important: their work showed the ductal system is critical to cancer development. In line with this, in a series of papers in the Nature family of journals, the laboratory homed in on common mutations which may provide hope for early treatment, when and if detected in time.

“Pancreatic cancer might be the best example showing why we need to study the evolution of cancer,” he said. “It’s aggressive nature means it’s a killer. There’s this biological window though, where we could treat it if we caught it early enough. My question is, what are we missing?”

Makohon-Moore came to the CDI to start his own laboratory, and further explore the many branches of evolution in cancer - not just pancreatic, but also other solid tumors and hematological malignancies .

The bioreactor is Makohon-Moore’s ingenious way of assessing the many variables when it comes to cancer’s evolution  in all its many forms. In April, the scientist had the bioreactor’s various components rigged to study a certain line of lymphomas, lymphoblastoid  cells, and a few organoids from another CDI lab’s work. These were arranged for different variables; in particular, the lymphoma cells were being tested for growth against starvation conditions which come close to mimicking a physiological  environment, versus nutrient-rich surroundings.

Contrary to intuition, starvation does not always kill the cancer - and complete nutrition is not always a catalyst for growth. Depending on the stage of development and a host of other factors Makohon-Moore and colleagues are assessing, one factor could either kill or exacerbate the tumor cells. The complexity is immense - but so too is Makohon-Moore’s ambition to plumb the secrets there.

“Finding out - that’s the task,” he said. “What happens when we pressure that cell - and how can we make that work to the benefit of a patient?”

Over his years of work, Makohon-Moore has pinpointed genetic commonalities among metastases. Some of this work led to the creation of new software tools to assess cancer's overall evolutionary strategy, of a kind. This work led to a pair of notable papers in Clinical Cancer Research, among other publications.

 LAB LIFE, FAMILY LIFE

He still works with his mentor, and he’s struck up collaborations with the other scientists investigating cancer at the CDI, since the work is so complementary. He’s recently received some distinctions for his trailblazing work, including a American Association for Cancer Research NextGen Award, and being named to the editorial board of the journal Cancer Research.

While establishing and running his first independent laboratory has been a huge time commitment, what free time he has is spent, in part, on reading and running, two of his great life-long pastimes. But family time comes first these days - he is married, with a four-month-old daughter and a precocious four-year-old daughter who has already expressed curiosity about cells and biology, and what he does when he’s at work.

“Family time is everything,” he said.