Mickey and I quickly connected based on our mutual interest in creative, out of the box approaches, in this case focusing on science and medicine. Mickey had just finished sonifying the vibrations of the cosmos, and we had just used new Nobel Prize-winning stem cell technology from the Gladstone Institutes to generate heart and brain cells from humans with patients with diseases of those organs. Heart and brain cells have a lot of electrical activity that we routinely record. Together with Mickey, we had the idea that converting the electrical activity of normal and diseased human cells to sound might reveal differences in the cells the could serve as flagposts of the disease state. As recorded in this new CD, Mickey's group has sonified heart cells provided by my lab and brain cells from Dr. Steve Finkbeiner's and Dr. Anatol Kreitzer's lab, all at the Gladstone Institutes. We can now test whether sound can "entrain" human cells to better state, and whether new therapies can be developed with the integrated sound output of human cells as a measure of success. I am thrilled to contribute to this CD, which represents a first for me in my years of science and medicine.
The human brain is a complex organ composed of billions of brain cells intertwined through trillions of connections with one another. Disruption of these networks underlies many devastating brain diseases like Alzheimers, Parkinson's and Hunington's disease, affecting millions worldwide. To better understand how the human brain cells work, human stem cells were generated by inducing skin cells from patients to turn into stem cells that have the capacity to become any one of the over 200 cell types of the human body. These stem cells, termed induced pluripotent stem (iPS) cells, were coaxed into becoming brain cells in a dish. The electrical signals induced by communication between connected brain cells were measured. Over 50,000 values of electrical measurement were integrated to generate the sounds of human brain cells grown in a dish for this album. Interestingly, the types of brain cells affected by Alzheimer's Disease and Parkinson's Disease displayed unique sound "signatures" and are part of this CD.
The heart is the metronome of human life. It rhythmically beats 3 billion times over a lifetime, never taking a break or missing a beat. But heart disease, the number one cause of death in men and women, disrupts this rhythm and can change the intrinsic electrical activity of the heart muscle cell. To understand how electrical activity in human heart cells is affected, we induced human skin cells from patients to turn into stem cells that have the capacity to become any one of the over 200 cell types of the human body. These stem cells, termed induced pluripotent stem (iPS) cells, were coaxed into becoming beating heart cells in a dish. Millions of heart cells contact one another and can beat rhythmically and in synchrony, like the human heart. We recorded the electrical signals from these beating human heart cells at baseline and after administering a drug to slow the heart rate. The electrical signals were converted to sound that integrated the many cellular events leading to rhythmic beating, and set the stage for detecting the sounds of abnormal heart cells that have rhythmic disturbance.
Dr. Srivastava’s research interests include understanding the causes of heart disease and using knowledge of cardiac developmental pathways to devise novel therapeutics for human cardiac disorders. His laboratory studies the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. These pathways may be useful in preventing congenital defects and treating acquired heart disease, particularly with cardiac-specific differentiation of embryonic stem cells. Dr. Srivastava’s lab has leveraged knowledge from developmental biology to reprogram non-muscle connective tissue in the heart directly into cells that function like heart muscle cells for regenerative purposes. Dr. Srivastava is also interested in identifying the causes of human cardiovascular disease by applying modern genetic and stem cell technologies. Such approaches to model disease in human cells promise to yield new therapies, and Dr. Srivastava has co-founded a biotechnology company to help find new cures for many human diseases.
Researchers in Dr. Srivastava’s laboratory have revealed a network of transcriptional, translational and signaling events that control the early steps of cardiomyocyte differentiation and expansion, including those involving microRNAs. His laboratory has used human genetics to discover the cause of some human cardiac septal defects and valve diseases, revealing that mutations in genes that control key networks result in cardiac anomalies. One of the developmental genes has potent properties for cardioprotection and is currently in clinical trials for patients suffering ischemic damage to the heart. Dr. Srivastava’s laboratory has trained more than 35 postdoctoral fellows and graduate students.
Before joining Gladstone, Dr. Srivastava was a Professor in the Department
of Pediatrics and Molecular Biology at the University of Texas Southwestern (UTSW) Medical Center in Dallas. He has received numerous honors and awards, including endowed chairs at both UTSW and UCSF, as well as election to the American Society for Clinical Investigation, the Society for Pediatric Research and most recently to the American Academy of Arts and Sciences. In 2012, Dr. Srivastava presented the prestigious George E. Brown Memorial lecture to the American Heart Association.
Dr. Srivastava completed his medical training at the University of Texas Medical Branch in Galveston and his residency in the Department of Pediatrics at UCSF. He also did a fellowship in pediatric cardiology at the Children’s Hospital of Harvard Medical School and a postdoctoral fellowship at the M.D. Anderson Cancer Center in Houston as a Pediatric Scientist Development Program fellow, before joining the faculty at UTSW in 1996.