Scientist Profile - Dan Salomon

Using the explosion of knowledge made available from the human genome project, Scripps Research associate professor Daniel Salomon, M.D.'s research is focused on using the latest technologies to advance the genomics, proteomics, and genetics of kidney, liver, and islet transplantation. Transplantation of organs such as kidneys, livers, hearts and lungs save thousands of lives each year. Dan's studies involve patients with kidney, liver and islet transplants and diseases such as kidney failure, diabetes, hepatitis, and cancer.

"The main objective of our lab is to advance our understanding of cell and organ transplantation in ways that will yield direct benefit to patients with diabetes mellitus, kidney and liver transplants," said Dan.

Dan and his colleagues have been monitoring several hundred patients who have had kidney and liver transplant surgeries with technologies for gene expression profiling and proteomics, and several thousand transplant patients by complex trait genetics.

One of his goals is to answer one of the most pressing problems in kidney transplantation: why do some patients do well after a transplant and others do not? "Fifty percent of transplant patients lose their kidneys within ten to twelve years," said Dan. "We're studying some 2,400 patients with kidney transplants, and are looking at the genetic basis and control of why some patients do well and others have problems."

In both organ and cell transplants, there is a danger of both infection and transplant rejection, arising from the fact that a donated organ or cell is foreign to the transplant patient's body. Left alone, the person's immune system will detect the foreign tissue and mount an immune response, killing the new tissue, and leaving the patient no better off than before the transplant. Wishing to avoid transplant rejection, doctors treat patients who have had transplantation with a powerful class of drugs, known as immunosuppressants, which weaken the immune response and mitigate the danger. With adequate doses of immunosuppressant drugs, a transplanted organ can survive and function well for decades. However, these drugs make transplant patients more likely to suffer heart disease, diabetes, infection and cancer, and can slowly poison the very kidney they are protecting in kidney transplants or lead to liver transplant patients requiring a kidney transplant after five to ten years.

Because of all the drug toxicities, one of the major challenges in treatment following transplant surgery is to determine the proper regimen of drugs needed for a patient. Patients must be given a strong enough dose of drugs so that their immune systems are kept in check. At the same time, they cannot receive so high a dose that the drugs are too toxic. Only with the right balance is successful transplantation achieved and the many risks minimized.

"Unfortunately the reality," says Dan, "is that there is no metric, no blood test, for adequate or safe immunosuppression. As a consequence, doctors are forced to determine immunosuppressive drug doses and combinations based on only published results from large trials and their clinical judgment and experience. This is a critical aspect of medicine but we have learned the tremendous value of objective tests that can identify the individual nature of each patient and their response to a drug or a drug combination."

Dan would like to change that and is hopeful that he can within the next couple of years. He is using the discoveries of genomic science to build a new set of tools so that doctors can measure and predict with a blood test how a patient will respond to immunosuppressive drugs. With such tools, transplant doctors could monitor patients regularly to make sure their treatment is always optimal and maximally safe.

There are two central theories being tested in Dan's work. The first theory is that there is a genetic "signature" within donors and recipients that predict the best course of treatment following a transplant surgery. This first signature is fixed by our genetic inheritance and the choice of a particular donor for a recipient. The second theory is that there is a genomic signature in the blood that at any given moment reflects the level of immunosuppression and the status of the immune response to the transplanted cells or organ. The genomic signature in blood is constantly changing and reflects the dynamics of health and disease. Dan is working on understanding both signatures and developing ways to detect it within the laboratory. He has made progress, showing for the first time that one can diagnose acute rejection and chronic rejection by profiling gene and protein expression in the peripheral blood using high density DNA microarrays and tandem mass spectrometry proteomics.

"We're applying multiple new technologies to understanding how to diagnose, manage patients, and improve the safety of therapies to organ and cell transplantation," said Dan. "In all our work, the objective is to work in a multi-dimensional genomic space created by an ongoing and iterative integration of the latest technologies with cell-based preclinical animal models and human clinical studies."

One unique feature of Dan's research is that all the genetics are done on both the patients and their kidney donors. "The genetics of the patient receiving the kidney determines the character of the immune response, but it's the genetics of the donor that determines the impact of the transplantation," said Dan. "What we're hoping to come out with is an understanding of what makes a good donor and what is it about the donor organ that determines the long-term outcome of the transplant."

Dan is particularly appreciative of the many new technologies and collaborations available at Scripps Research. "We have powerful cutting-edge technologies for genomics, proteomics, animal model building, cell biology and small molecule discovery which speed research," he said. "My research is constantly drawing on these resources."

One of Dan's patients is Mark Baber, an ex-Microsoft executive originally from the Seattle area. After Mark and his wife Molly, a successful AT&T executive, moved to San Diego, Dan took over care of Mark's kidney transplant that he received just before moving because he is a diabetic. Mark and Molly struck up a friendship with Dan and learned about his research. Before Molly's sudden and tragic death from a cerebral aneurysm, she and Dan were working on a fund to support research in his laboratory on transplantation and diabetes. In her memory, Mark created the Molly Baber Research Fund for Diabetes and Transplantation Medicine.

"In lieu of flowers, I asked people to contribute to the fund at the memorial service," said Mark. "I knew it was something that Molly would have wanted to have done." Mark has done a couple of fundraisers recently for Dan's research and has now forged a relationship with the William Church Winery of Woodinville, Washington, in which the winery is donating $1.00 for every bottle of their new cabernet sold to the Molly Baber Research Fund.

"I think this is a remarkable gesture to support medical research here," said Dan. "It was my pleasure to know Molly and experience her incredible sense of life and unselfish commitment to helping people. In creating this research fund, we are honoring her spirit and dedicating our research to her passions for health, scientific and human understanding, integrity and excellence."

"When you're a diabetic since age 11, you have a long exposure to different doctors," said Mark. "What I've noticed about Dan is that he is not only an incredibly talented and gifted physician and researcher, but he has the unique ability to talk to a patient in almost a peer-to-peer way. His sensitivity stands out." Dan has also earned the admiration of his colleagues. "Dr. Salomon is a great mentor and an amazing person," said Staff Scientist Stephanie Cherqui, Ph.D., who works in Dan's lab.

Dan was formerly the Medical Director of the Kidney and Heart Transplant Programs at the University of Florida. He later moved to the National Institutes of Health (NIH). He came to Scripps Research in 1993.

"I had visited a collaborator from Scripps Research while I worked at the NIH," said Dan. "I liked the focus of basic science and how people were really driven to work collaboratively here. I saw the tremendous potential of working in such a science-based environment to create translational research, moving basic discoveries from the bench to the bedside where they can help people live healthier and more productive lives."

Dan was a chemistry major at Northwestern University, received his M.D. from Stritch-Loyola School of Medicine in Chicago, trained at Cedars-Sinai/UCLA for internal medicine and did his postdoctoral work in transplantation and immunology at Harvard Medical School. While he modestly shakes off his many honors, there is a recent one that he is particularly proud of - being inducted into the Alpha Omega Alpha Society, a medical honorary society which is the equivalent of Phi Beta Kappa, by the Stritch-Loyola School of Medicine.

"The school had tracked my work," said Dan. "They were impressed with both the basic bench research and the translation to bedside that it entailed. I was invited and gave several lectures on campus and addressed the graduating class. It was a wonderful honor and very meaningful to me, and it was great to be given the opportunity to stir and challenge the young minds of future physicians and scientists."