Prof. Mohamed El. Sayegh

The One of a Kind Leader

Mohamed H. Sayegh; an Intimate Profile

As Paracelsus, the Swiss medieval physician, said quite rightly, “medicine is not merely a science but an art. The character of the physician may act more powerfully upon the patient than the drugs employed.” This character, or a physician’s influence on the patient or his/her co-workers, makes a huge difference. This is why a medical student should improve his/her leadership skills besides learning the clinical aspects of care.

Dr. Mohamed H. Sayegh plans to write a book on leadership. “I spent the last 11 years of my life as Dean of medical school and as an executive in healthcare. I learned a lot about leadership,” he says. He is indeed an eminent leader who has served the last decade as the Dean of the Faculty of Medicine and Executive Vice President of Medicine and Global Strategy at the American University of Beirut (AUB), Lebanon. “After spending 22 years of my academic career as a physician-scientist, this senior-level leadership role shaped the next phase of my academic career. I was responsible for around 5,000 health care professionals,” he says.

Leaders’ performance comes into focus when the situation is of an emergency, and it is most common to be stuck in an emergency when you choose medicine as your career. Anyone who witnessed a surgery gone awry in an operating room appreciates the value of efficient leadership. In medical practice, leaders can take the group performance to higher levels of excellence at any level of the organizational chart by inspiring the staff and encouraging them. They know how to manage the team to stay on a mission in a stressful situation.

Good leadership is based on the wisdom derived from many years of actual failures and successes in the field. “Good leadership is about team formation, caring, mentoring, and creating future leaders,” Dr. Sayegh says. He thinks the essential skills a leader should possess to maximize group performance include “teamwork, functional working groups rather than rigid hierarchy, and investing in the Human Resources.”

He plans to write a book on medical leadership, with “The One of a Kind Leader” as its title, to emphasize that leadership, first of all, is about creating future leaders. It is not surprising that he likes a quote from the American writer Ralph Waldo Emerson that “Do not go where the path may lead. Go instead where there is no path and leave a trail.”

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Mohamed H. Sayegh is the 10th and the last child of a large family living in Beirut. “I grew up mostly with my nephews and nieces,” he says. He was a city boy accustomed to urban lifestyle but enjoyed picnics and outings with family and friends or through school planning.

Sciences, History, and Arabic literature were his favorite subjects in school. Arabic poetry is still his favorite pastime. The white medical gown, however, was the future garment he envisaged himself in. “I grew up in a family where my older brother was a doctor. When I was young, he was in the States, and he was our idol. I always knew I wanted to be a physician but was not sure about research and discovery until later.” He says.

Mohamed H. Sayegh, following the example of his elder brother, moved to the United States after receiving a medical doctorate from the American University of Beirut in 1984. In the United States, he first completed his Internal Medicine residency at Cleveland Clinic Foundation in Ohio by 1987, and then his clinical fellowship in Renal Medicine and Transplantation Immunology at Harvard Medical School and the Brigham and Women’s Hospital in Boston by 1990. He taught in Harvard Medical School from 1990 to 2009, where he ascended to Full Professor of Medicine and endowed a chair in Transplantation Medicine.

In the July of 2009, Dr. Sayegh returned to his alma mater, the American University of Beirut, as the Dean of the Faculty of Medicine and the Vice President for Medical Affairs. Besides this, he holds many executive positions and is serving as a special advisor to several high-profile projects.

Dr. Sayegh has received many prizes, awards, and honors in the past four decades, including a mentoring award from the American Society of Transplantation in 2008. He is a member of many learned societies, such as the American Society of Transplantation, which served as its president from 2000 to 2001.

Dr. Sayegh is a prominent researcher and a world-renowned pioneer in fields concerning nephrology, organ transplantation, and transplantation immunology. “When I was doing my internal medicine residency in Cleveland, I was intrigued about research. I got interested in transplantation immunology,” he says.

Dr. Sayegh, a member of many high-impact medical journals editorial boards, has helped these fields proceed through his contributions such as journal publications, book chapters, and a few textbooks.

Dr. Sayegh is pursuing an ambitious plan in the American University of Beirut Medical Center, known as the AUBMC 2020 Vision, which has reversed the brain drain process in the last decade by bringing back more than two hundred Lebanese medical researchers from abroad.

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Dr. Sayegh names his wife, Dr. Samia Khoury, as one of those persons who have the most significant influence on his career. Dr. Khoury is herself a professor at the American University of Beirut and a world expert on multiple sclerosis.

Dr. Sayegh thinks he owes much to his mentor at Harvard, the late Dr. Charles B. Carpenter (1933-2012). “Bernie had a big influence on me,” Dr. Sayegh says. Dr. Carpenter, or Bernie to those close to him, was a part of the team that performed the world’s first kidney transplant and a founding member of the American Society of Nephrology, and the American Society of Transplantation, among others. However, Dr. Carpenter, who has been described as a “true pathfinder in the field of transplantation and nephrology,” is mostly remembered as a great mentor to generations of leaders in the field – a niche Dr. Sayegh is determined to occupy.

Dr. Sayegh is a credible calm leader, one that listens patiently to those who come for advice. He is all that it takes to be a great mentor and, through the years, has trained many researchers who are now themselves leaders of renal transplants around the world. “Dr. Sayegh has shown leadership skills very early in his career. His colleagues always sought his advice and guidance. His greatest attribute is his mentorship. He has been a wonderful mentor to many people,” says Dr. Khoury.

Dr. Sayegh has made mentorship his trademark. He is the new Dr. Carpenter to the next generations. It seems the mentorship is something that can at least be caught even if it cannot be taught.

Struggle for Tolerance in a Hostile World

Dr. Mohamed Sayegh Search for Immunologic Tolerance to Avoid Transplant Rejection

Some while ago, a friend of Dr. Mohamed Sayegh, “a nephrologist, a colleague and a friend of the family,” passed away after the complications of a kidney graft he had received from his wife many years ago. It seems that rejection, acute or chronic, is the final fate of any transplant, and the recipient should expect it sooner or later.

Dr. Sayegh is “interested in understanding the mechanism of transplant rejection and how to fool the immune system to accept the transplant, a term called immunologic tolerance.” His team has even used transgenic animals to study the mechanism of rejection and tolerance. Dr. Sayegh is mostly focused on promoting research at the regional level nowadays.

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Donating one of your kidneys does not shorten your life expectancy, but it may add up to 20 happy years to the lifespan of those with kidney failure. It is the most promising, and most of the time the only, therapeutic measure for a so-called end-stage renal patient with irremediably dysfunctional kidneys.

The American surgeon Joseph Murray (1919-2012) performed the first successful kidney transplant in 1954, which brought him the 1990 Nobel Prize in Physiology or Medicine. In that revolutionary transplant surgery, the recipient received a kidney from his twin brother, which gave him another eight long years to live.

This so-called isograft is a type of transplant in which the donor and the recipient are not the same but are genetically identical. Isograft is technically a kind of allograft, or a graft from another person, but is immunologically similar to autograft, or a graft from the same person, in that it does not trigger an immune response.

However, not everyone has a twin willing to donate a kidney to his/her sibling, let alone for other organs that have no extra copy that could be spared. Limiting the kidney grafts supply to a diminished source of genetically identical twins would not answer the huge demand for organ or tissue transplants.

Today, about 100,000 kidney transplant surgeries are performed worldwide every year, up to 60% of all transplant surgeries followed by liver, heart, and lung, respectively. Though the kidney transplant is the most common transplant surgery, it has the longest waiting list, too, with more than 5 people for each available kidney.

The main hurdle that should be passed somehow is a problem called histocompatibility, or tissue compatibility, having similar genetics for cell surface protein. Immune cells check these proteins to discern if the cells carrying them on their surfaces belong to their own body or an invading foreign organism. In the latter case, the graft would be rejected by the recipient’s immune system.

The rejected graft would be destroyed and lose its function. Routine clinical procedures include testing a potential recipient’s compatibility to an available organ and using immunosuppressant drugs.

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Let us have a look at the immunology of transplants. The alloresponse -- in which the prefix “allo-” from Greek means other and different -- is the immune system response to different cells and tissues belonging to other individuals. For such a response, the immune system must first recognize the foreign or allogenic molecules by a mechanism called allorecognition, short for alloantigen recognition. An organism defends itself against any potential invader through this phenomenon that has been observed in all vertebrates and other multicellular animals. The recognition is done using molecules called antigens on the surface of the non-self cells.

There is much polymorphism in these surface proteins called the major histocompatibility complex (MHC) molecules. If the molecules are genetically dissimilar, they are immunologically incompatible and will be recognized by the recipient’s immune system. As the term histocompatibility implies, MHCs were first discovered in the process of tissue transplantation between individuals with incompatible genetics: The donor cells had MHCs on their surfaces that were incompatible with host cells.

In humans, T-cells or T lymphocytes, a kind of white blood cells, are in charge of distinguishing between self and non-self cells antigen. Allopeptides bound to MHC molecules are displayed on the surface of antigen-presenting cells (APCs) to be recognized by T-cells. In transplantation, T-cells recognize the foreign antigens of the donor’s cells and react accordingly. This is where the graft rejection process begins. Even a minor incompatibility may provoke a strong reaction from host T-cells.

Recognition by T-cells takes place directly or indirectly, depending on the allograft characteristics. In the direct pathway, recipient T-cells recognize the allogeneic MHC molecules expressed by APCs of the donor as foreign. These cells that display non-self allogenic antigens -- MHC-peptide complex -- on their surface, exit the grafted organ soon after transplant and reach the host T-cells through the lymphatic system and teach them directly about their potential targets.

However, the recognition may occur indirectly when recipient T-cells recognize a self MHC molecule bound to a peptide with different amino acids. The alloantigens from graft are internalized, after engulfing surface proteins of donor cells by the recipient APCs, and then presenting them in the form of peptides on their MHC molecules. These “wrong” peptides, or allopeptides, will be presented on the recipient APCs, not the donor APCs, as is the case in the direct allorecognition.

Both direct and indirect allorecognition may be involved at the same time in allograft rejection. Direct allorecognition often leads to acute rejection of allografts soon after transplantation, while indirect allorecognition often contributes to chronic rejection in the long-term through damaging the graft with progressive loss of function that leads to graft loss finally.

The indirect pathway of allorecognition leading to chronic allograft rejection is the subject Dr. Sayegh and his colleagues have researched thoroughly in the past decades. They have devised, among others, a clinically useful novel assay that shows the occurrence risk of indirect allorecognition and chronic rejection in humans and then developed specific therapeutic strategies to prevent or interrupt this process.

For transplantation to be successful, the human leukocyte antigen (HLA) of the donor and the recipient must be the same, which is seldom the case. Even a minor HLA mismatch, which is actually unavoidable, leads to allorecognition and increases the risk of graft rejection. “We examined the response to incompatible HLA peptides as a predictor of chronic rejection,” Dr. Sayegh says.

Immunology is a hostile world; a cell eats cell world, to use Thomas Hobbes analogy. It takes a savior and brilliant approach to bring tolerance to such a milieu. Dr. Sayegh believes that the most critical question in the field is “the mechanism of immunologic tolerance and how to fool the immune system to accept a foreign organ without rejection and immunosuppression.” This would revolutionize tissue and organ transplantation. “This is still elusive,” he says.