Most people don鈥檛 think about their pancreas very often. Buried deep inside the abdomen, wedged between the stomach and the spine, we can鈥檛 even feel it. But there it is, day in and day out, working away to make the enzymes that digest our food and the hormones that control our blood sugar. Having a healthy pancreas is a great thing.
A healthy pancreas is maintained, in part, by a specialized group of cells: pancreatic stellate cells (PSCs). PSCs aren鈥檛 the cells that make enzymes or hormones, but they鈥檙e just as important. When dormant, PSCs quietly provide the pancreas with structural support. When activated, for instance by injury or illness, PSCs repair the pancreas by secreting extracellular matrix (ECM) proteins, cytokines, and growth factors.
Despite their seemingly benevolent disposition, take a closer looks and you鈥檒l find that PSCs have a sinister side. Cancer cells also activate PSCs to secrete ECM proteins, cytokines and growth factors. Within the context of pancreatic tumors, these factors have adverse effects: they drive the growth and proliferation of cancer cells and give the tumors a dense, fibrous makeup, making them notoriously difficult to treat.
The connection between PSC activation and pancreatic tumors has only recently been established. There is still much to learn about how the environment surrounding pancreatic tumors鈥攖he so-called microenvironment鈥攁ffects cancer progression and treatment, and Watson School of Biological Sciences (WSBS) third-year student Abram Handley-Santana has made it his goal to do just that.
鈥淧rimarily, I鈥檓 concerned with understanding how pancreatic cancer cells communicate with PSCs,鈥� said Abram. 鈥淚t鈥檚 the 鈥榟ow鈥� and 鈥榳hy鈥� behind pancreatic tumor growth.鈥�
Abram, working in Dr. David Tuveson鈥檚 lab at 黑料吃瓜资源, said that he spends most time working with pancreatic tumor organoids and performing tissue culture. Such ex vivo research makes it possible for him to identify factors that are induced when pancreatic cancer cells and PSCs are grown together. Abram wants to explore the effects of these factors on pancreatic organoid and PSC biology, eventually validating their roles in animal models and in human cells.
鈥淚 take PSCs that have never seen pancreatic cancer cells, mix them with pancreatic cancer cells, wait, watch and see what happens,鈥� explained Abram. The pancreatic cancer cells used in his experiments come from either human pancreatic cancer patients or mice genetically modified to develop pancreatic cancer.
Abram has been interested in studying cancer since his time as an undergraduate at the University of California, Santa Cruz. Initially, Abram planned on earning his bachelor鈥檚 degree in chemistry, but, after taking an introductory biology class, Abram realized he was much more interested in that field and changed his major as a sophomore.
When he came to WSBS, Abram knew he wanted to study cancer. Before the first semester, he worked with Dr. Lloyd Trotman, studying the tumor suppressor PTEN, where he said he gained a new experience with cloning techniques and how to work independently in a lab. He rotated in Tuveson鈥檚 lab, where he is now, studying pancreatic cancer; the lab of Dr. Mikala Egeblad, where he studied breast cancer; and Dr. Mickey Atwal鈥檚 lab, analyzing genetic interactions in cancer genomes.
Working in those labs has provided Abram with the skills necessary to be a successful cancer scientist. 鈥淲orking with Dr. Tuveson has increased my proficiency in performing tissue cultures and using the microscope,鈥� said Abram. 鈥淚n Dr. Egeblad鈥檚 lab I learned imaging techniques鈥攚hich are really interesting鈥攁nd in Dr. Atwal鈥檚 lab I had the opportunity to learn and perform computational research, which was new for me.鈥�
The Tuveson lab works to understand the basic biology behind cancers鈥攑rimarily pancreatic cancer鈥攚ith the aim of developing new diagnostic and therapeutic strategies. In the case of Abram鈥檚 research, potential treatments might target PSCs to decrease their production of fibrous tissue, cytokines, and growth factors, which together could slow tumor progression and enhance the delivery of chemotherapeutic agents to the tumor.
Abram said he is excited to continue his research in the Tuveson lab, which would contribute to the growing body of knowledge of PSCs and their role in pancreatic cancer. Though he acknowledges that gaining a better understanding of PSCs could lead to more effective pancreatic cancer treatments, Abram is concentrating on his immediate goals.
鈥淩ight now I鈥檓 focused on earning my Ph.D. and on becoming a better scientist. I strive to do my best in the lab each day,鈥� said Abram, who plans on returning to California to work in the biotechnology industry after graduation. 鈥淚 believe gaining a mastery of the basics can lead to a big discovery down the road.鈥�