Piero Dalerba, M.D., is a physician at heart. Helping patients has always been his passion.
The doctor, who earned his medical degree at the University of Milan in Italy, trained as a medical oncologist and has received a series of distinctions since 1995. But over the years he has realized he enjoys “dabbling,” as he puts it, in science. Fortunately for Hackensack Meridian Health, that “dabbling” has led to some groundbreaking research regarding the discovery of new biomarkers that can be used to guide cancer cells.
With a desire to further explore this research and impact lives, he joined Hackensack Meridian’s Center for Discovery and Innovation (CDI) from Columbia University earlier this year as an associate member.
“What really excites me is the possibility to change medical practice and improve clinical outcomes for cancer patients,” said Dalerba. “The CDI is designed to function as a catalyst for research aimed at bringing scientific discoveries into practice. At the CDI, scientists can connect with a large network of world-class clinicians, leverage their collective expertise and work together to benefit a large and diverse patient population, in a research environment that is not only technologically advanced, but also permeated by a collegial spirit. This is what attracted me to the institution.”
“Piero Dalerba’s work is exciting, and a great complement to so much of the other groundbreaking research at the CDI,” said David Perlin, Ph.D., the chief scientific officer and executive vice president of the CDI. “His initiative embodies CDI’s innovative philosophy.”
The Dalerba Lab at the CDI
The goal of the scientists in Dalerba’s lab is to advance cancer treatments through a better understanding of the role played by epithelial stem cells in the origin of a variety of human malignancies. That includes colon cancer, breast cancer and aggressive cancers of the salivary glands. Through learning more about how these tumors work and respond to medication, they hope to help develop innovative anti-tumor drugs.
His team works under the firm belief that, in order to cure cancer patients, it’s not enough to develop drugs that can shrink tumors. Doctors must also develop drugs that can eliminate cancer cells with a stem cell phenotype (“cancer stem cells”), which often represent a small sub-group of cells, but stand at the root of cancer development (and can “reboot” cancer growth after chemotherapy).
Since arriving at the CDI, Dalerba and his team focused on the discovery of biomarkers that are predictive of tumor response to anti-neoplastic drugs, in order to improve therapeutic guidelines and decision-making algorithms for cancer patients. His team uses single-cell technologies, such as single-cell RNA-sequencing, to deconvolute the cell composition of cancerous tissues and identify drugs that are most effective in eliminating specific sub-types of cancer cells.
He explains, in layman's terms, the theory behind his studies:
“We basically think of tumors as caricatures of normal tissues. Tumors originate from normal tissues, and “emerge” as a progressive corruption of their developmental programs. So you can think of cancer mutations as mistakes, or ‘typos,’ in the software code that controls tissue development, which leads to the formation of abnormal organs. Within such abnormal organs, different types of cancer cells co-exist, and can change one into the other, in a dynamic fashion, following biological programs similar to those that enable stem cells to repair normal tissues after they have been damaged. In our laboratory, we try to discover drugs and biomarkers that are specific to cancer cells that behave as ”cancer stem cells”.
Dalerba also added that being at the CDI has been a new high point in his career, because the opportunity is there to accelerate the evolution of standards of care - and transform patient lives.
“What attracted me to the CDI and HMH is the possibility to ‘connect’ with an immense medical network that is, at the same time, home to a cutting-edge academic center and squarely focused on patients, clinical care and translational research,” he said. “Research that is aimed practically at improving therapeutic algorithms and treatment guidelines, at rapidly translating into practice the discoveries made in the laboratory. The opportunity to network with clinicians and access their wealth of knowledge and clinical expertise is really what makes HMH such a fantastic place.”
From Italy to the CDI
Before moving to the United States to pursue a career in science, Dalerba trained as a physician - the first in his family. His mother was a math teacher and his father was both an engineer and art historian. Dalerba says he learned the importance of problem solving and developing solutions from both of his parents. And in its purest form, that led to his desire to help heal patients on two continents.
It was during medical school in Milan, Italy, that Dalerba’s fascination with modern genetics developed.
“When I started medical school, I was so impressed by the advances made by modern molecular genetics, especially when it came to explaining the mechanics behind the origin of so many diseases – a single point mutation in a single gene could initiate a chain reaction of deleterious effects, affecting a multitude of tissues and organs, translating into complex constellations of symptoms, and ultimately causing so much pain,” he recalled. “And it was so inspiring to witness how some of these patients could be cured, sometimes by simple dietary adjustments or elegant pharmacological interventions, once, and only once, you had an understanding of the molecular mechanics underpinning the disease.”
Inspired to continue his studies in America by his Italian mentor, Dr. Giorgio Parmiani, he met and married an American scientist. They have a daughter and live in New York. Throughout his lengthy and impressive career that’s covered both Europe and the United States, Dalerba’s mission to ultimately find potential cures for cancer has never wavered.
“We have so much power in terms of changing the trajectory of the lives of patients in such fantastical ways”, he said. “It was such a mesmerizing and powerful call. Aside from the intellectual pleasure of discovery, there is this incredible reward in terms of really potentially curing patients with complex diseases. It was a great calling, and I decided to follow it.”
Published Articles and the Future
Dalerba gets very passionate about studies ongoing in his laboratory. One of his most important papers was recently published in the Journal of the National Cancer Institute. And it’s carving a path for a promising new treatment for adenoid cystic carcinoma (ACC), an aggressive form of malignancy that often originates from the salivary gland. Dalerba discovered two biomarkers that enable investigators to purify two subtypes of malignant cells co-existing in the tumor tissue. These two types of cells are linked by a “mother-daughter” relationship. Dalerba's team identified a new class of drugs that, on the one hand, selectively kills the daughter cells and that, on the other, prevents mother cells from generating new daughter cells. He hopes that this new class of drugs will halt the progression of cancer.
“One of the directions that I would like to pursue is to develop these drugs as medicines that can be used in the real world, and test whether they can be helpful also in the treatment of breast cancer,” he said.
In 2016, Dr. Dalerba and colleagues also published research in the New England Journal of Medicine, identifying a biomarker that can be used to predict which colon cancer patients will most likely benefit from chemotherapy administered after surgery to prevent cancer recurrence. (colon cancer has thus become a major focus of Dalerba’s experimental work).
Dr. Dalerba’s research has been supported by grants from a variety of funding agencies, including the U.S. National Institutes of Health (NIH). But he has also been supported by non-profit foundations, such as the Adenoid Cystic Carcinoma Research Foundation (ACCRF) and the Damon Runyon Cancer Research Foundation, which provided seed funding for his experiments.
What free time Dalerba has away from the laboratory is spent with his wife and daughter, perhaps hiking in the Catskills and in the Hudson Valley. The cultural offerings of Manhattan are also something he values: from visiting the museums, the theater, and occasionally hunting for antique books, as time allows.
So what’s next for this ground-breaking scientist at the CDI?
Now that his research operation at the CDI is well underway, Dr. Dalerba plans to spend more time getting to know the oncologists within the HMH community to share ideas, specifically as they relate to colon cancer treatment.
“I now have the opportunity to interface with world-class medical oncologists in a collegial and collaborative environment, where we can sit-down and work together to design clinical trials. Truly, this is my big dream. To cross the final bridge and bring many years of science to practical benefit.”