Research Day Highlights Hearts and Minds

Cardiologist Christine Seidman, MD, of Harvard Medical School lectures at Research Day VIII.

Christine and Jonathan Seidman lend new meaning to William Shakespeare's poetic paean to love: "the marriage of true minds." As co-directors of the pioneering Seidman Lab at Harvard Medical School, they are partners in both life and science. The Seidmans met in an undergraduate biology class at Harvard University and married in 1973.

Their longtime partnership has produced three children and reams of breakthrough research about the genetic causes of cardiovascular disease, including congenital heart malformations and cardiomyopathies — diseases of the heart muscle.

On Jan. 13, they shared their unique insights at an annual showcase of Cedars-Sinai's research achievements. Cardiologist Christine Seidman, MD, and geneticist Jonathan Seidman, PhD, delivered back-to-back keynote presentations at Research Day VIII to a capacity crowd in Harvey Morse Auditorium. Their talks were followed by a poster session displaying scores of collaborative research studies at Cedars-Sinai.

In introducing the Seidmans, Kenneth Bernstein, MD, director of Experimental Pathology and professor of Biomedical Sciences and Pathology and Laboratory Medicine at Cedars-Sinai, shared a comment by Christine Seidman about the duo's dual roles: "It's fun to have a good idea over the weekend and be able to go and talk to your closest scientific collaborator right then and there."

Jonathan Seidman chronicled the pair's investigations of congenital heart disease, the most common birth defect. "We wanted to understand its genetic basis," he said. Numerous Seidman-spearheaded studies and collaborations point to a genetic disruption during development of the embryonic heart as a cause of this disease.

The research also found that neurocognitive issues are common among children with severe congenital heart disease. These issues are attributable, in part, to genetic mutations that alter critical pathways for both heart and central nervous system development, they have shown.

"The same genes that cause congenital heart disease in kids also affect development of their neurologic systems," Jonathan Seidman said.

As Christine Seidman took her turn at the lectern, she acknowledged her husband's role in the genetics of congenital heart disease. "As an adult cardiologist," she continued, "I spend much more time thinking about the community of individuals who are born with a perfectly normal heart that deteriorates over time."

The Seidmans' research has prompted a major shift in views of one type of deterioration, dilated cardiomyopathy, a condition that reduces the heart's ability to pump blood. For a long time, this condition was thought to be caused by an infection or toxins. Skeptical of this view, the Seidman team turned its attention to an extremely important, but at the time largely uninvestigated, protein called titin.

Research lab assistant Lizbeth Sanchez discusses her research poster with Robin Shaw, MD, PhD (blue shirt), and Eugenio Cingolani, MD.

Titin is the largest human protein, containing more than 30,000 amino acids. The Seidman Lab became the first to take on the titanic task of sequencing the gene that codes this super-sized protein.

Showing a slide that encapsulated five years of work, Christine Seidman explained that the lab's study uncovered titin mutations. "These mutations are really driving dilated cardiomyopathy. That's the titin story, and it's something new and ongoing," she said. The Seidmans are further credited with demonstrating that all cardiomyopathies have a genetic cause.

"I hope we've provided evidence that genetics is incredibly important in human heart formation," Christine Seidman said. "With that insight, we are very optimistic that there's going to be a wealth of new therapeutics. In the future, if we can begin to recognize early those who have these mutations, then we can prime them with drugs that limit the mutations' development."

After the Seidmans' tag-team talks, attendees strolled through several aisles of research posters focusing on myriad medical topics, including epithelial ovarian cancer, hip disease, multiple sclerosis, non-small cell lung cancer, Parkinson's disease, prostate tumors and renal cancer.

The exhibit space buzzed with collegial conversations. A poster submitted by Lizbeth Sanchez, a research lab assistant in the Marbán Laboratory, for instance, sparked a lively discussion about converting heart ventricular cells into pacemaker cells and potentially using them to replace implanted electronic pacemakers.

Graduate student Kellee Murayama was interested in a research poster from fellow student Rachel Baum, whose study identified a decrease in the protein cBIN1 as a potential marker for advanced heart failure.

"It's good to walk around and see what other people are studying," Murayama said. Baum agreed: "Seeing all of the different studies also gives you ideas for possible collaborations," she said.

Three prizes were awarded for the best research posters:

  • First prize — Shirley Cheng, research lab assistant, for "Bio-Competition-based Smart NanoVelcro Chip for Isolation and Expressional Analysis of Circulating Tumor Cells from Prostate Cancer Patients," from the laboratory of Edwin Posadas, MD, medical director of the Urologic Oncology Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute.
  • Second prize — Eugenia Lin, clinical research coordinator for GI-Motility in the Cedars-Sinai Department of Medicine, Division of Gastroenterology, for "Examination of the Effects of Breath Hydrogen Levels on EC/IR II," from the laboratory of Mark Pimentel, MD, director of the GI Motility Program and GI Motility Laboratory.
  • Third prize — Graduate student Mecca Madany for "Delineating the Role of ZEB1 Loss in the Chemo and Radioresistance of Glioma Stem Cells," from the laboratory of Beth Karlan, MD, director of the Women's Cancer Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute.