Recap – LustgartenLive!: Where Tomorrow’s Breakthroughs Begin

A special LustgartenLIVE! highlighting three leading investigators who shared exciting research fueled by Lustgarten’s Innovation & Collaboration Program

Big breakthroughs often begin with a bold idea and the opportunity to pursue it.

During our latest installment of LustgartenLive!, a live-streaming symposium, three investigators supported through the Lustgarten Foundation’s Innovation and Collaboration Program shared how unconventional questions, new partnerships and early investment are opening promising avenues in pancreatic cancer research.

Moderated by Lustgarten’s Program Scientist Sejin Chung, PhD, the conversation featured Mandar Muzumdar, MD, of Yale School of Medicine; Linda Resar, MD, of Johns Hopkins; and Ronald Parchem, MD, PhD, of Baylor College of Medicine. Their research spans nutrition, tumor biology, immunotherapy and cancer neuroscience, with each project demonstrating how cross-disciplinary collaboration can uncover possibilities that might otherwise remain unexplored.

Now in its fourth year, the Innovation and Collaboration Program provides seed funding for high-risk, high-impact research, including work led by investigators bringing expertise from outside the pancreatic cancer field. These early investments can generate the preliminary data researchers need to pursue larger grants, build new collaborations, and move promising ideas forward. For Muzumdar, an Innovation and Collaboration grant helped generate work that ultimately led to a federal grant he estimated represented roughly a 20-fold return on Lustgarten’s initial investment.

Could the type of dietary fat influence pancreatic cancer risk?

At Yale School of Medicine, Muzumdar and his team are investigating a deceptively simple question: how do different dietary fats influence pancreatic cancer development?

Working with Yale fat biologist Matthew Rodeheffer, PhD, endocrinologist John Wysolmerski, MD, and postdoctoral fellow Christian Ruiz, PhD, Muzumdar is studying diets containing different sources of dietary fat.

In a mouse model of pancreatic cancer, the researchers found that diets enriched in oleic acid, a monounsaturated fat abundant in olive oil, promoted tumor development, while diets enriched in polyunsaturated fats, including those found in safflower and fish oils, suppressed it. Their findings suggest that the balance between different types of fatty acids, rather than total fat intake alone, may influence tumor formation.

The researchers also found that dietary fatty acids became incorporated into pancreatic cells, altering their susceptibility to ferroptosis, a form of cell death. Encouragingly, analysis of blood samples from a large UK cohort showed an association between the same fatty-acid balance and pancreatic cancer risk, providing early evidence that the mechanism could be relevant in humans.

These findings are not yet a basis for specific dietary recommendations. Instead, they raise new questions about whether precision nutrition could one day become part of pancreatic cancer prevention, particularly for people with an elevated risk due to genetics or family history.

Exposing how pancreatic tumors hide from the immune system

At Johns Hopkins, Resar is studying HMGA1, an oncogene her laboratory discovered and has linked to aggressive tumor behavior.

HMGA1 acts as a molecular switch, opening and closing regions of the genome in ways that help drive cancer. Resar’s research has shown that high levels of HMGA1 are associated with poor survival in pancreatic cancer.

Her Lustgarten-supported research has uncovered another important role: helping tumors evade the immune system.

Resar and her team found that HMGA1 activates FGF19, a growth factor that can be targeted with existing approaches. Blocking FGF19 through drugs or gene silencing slowed tumor growth. But the team also discovered that HMGA1 affects the tumor immune environment, suppressing signals that would otherwise help immune cells recognize and attack cancer.

The research has expanded through collaboration with Lustgarten Chief Medical Advisor Elizabeth Jaffee, MD, Won Jin Ho, MD, and pathologist Laura Wood, MD, PhD, combining spatial transcriptomics, sophisticated tumor imaging and patient samples to better understand these interactions.

Because the FGF19 pathway appears elevated in only a subset of pancreatic tumors, the team is working to identify which pathways are active in individual patients. The long-term goal is personalized immunotherapy: matching patients with treatments aimed at the specific mechanisms their tumors use to escape immune attack, rather than relying on a single approach for everyone.

What if pancreatic tumors build their own nervous system?

Parchem entered pancreatic cancer research from an entirely different direction.

A developmental biologist at Baylor College of Medicine, his career focused on how embryos build a nervous system. With support from Lustgarten’s Innovation and Collaboration Program, he began applying those tools and insights to pancreatic cancer.

What his team found was striking.

Neural stem cells, cells capable of generating components of the nervous system, persist in the adult pancreas along existing nerves. Pancreatic tumors, meanwhile, are much more densely innervated than healthy pancreatic tissue.

Parchem’s research suggests tumors do more than simply attract nearby nerves. They appear to reactivate developmental programs used during embryonic growth to build new nerve connections, with mutant KRAS playing an important role in triggering this process.

Working with collaborators including Anirban Maitra, MD, MBBS, of NYU Langone’s Perlmutter Cancer Center; Frank McCormick, PhD, of UCSF Helen Diller Family Comprehensive Cancer Center; and Benjamin Deneen, PhD, of the Baylor College of Medicine, Parchem has also connected this signaling to perineural invasion, the process by which cancer cells travel along nerves. Perineural invasion can contribute to pain, make tumors more difficult to remove surgically and play a role in recurrence.

The team is now investigating whether nerve recruitment begins even earlier, including in precancerous lesions known as PanINs. If it does, nerve-related changes could potentially help researchers distinguish lesions likely to progress to pancreatic cancer from those that may not.

The work could ultimately have implications across the cancer continuum, from controlling pain and limiting tumor spread, to identifying new opportunities for early detection and prevention.

Investing early to accelerate progress

These three projects tackle very different questions: How does diet affect the pancreas? How do tumors evade immune attack? Why are pancreatic tumors filled with nerves? But together, they demonstrate what can happen when scientists are given the resources to pursue unconventional ideas and the freedom to collaborate across disciplines.

At Lustgarten, we believe bold ideas, and the collaborations that bring them to life, are fundamental to changing what is possible for pancreatic cancer patients and their loved ones.