Dr. Ellen Gravallese: The Face of Translational Rheumatology

Dr. Ellen M. Gravallese has had a trail-blazing and award-winning career in which she has straddled rheumatology to make contributions both to the bench and the bedside. Her accomplishments owe much to her joint abilities to focus on basic research that bears fruit in the form of meaningful clinical improvements in patient management and to foster the next generation of rheumatology investigators. But there has also been a place for serendipity in her trajectory.

As director for translational research at the Musculoskeletal Center of Excellence, University of Massachusetts Memorial Medical Center, Worcester, Dr. Gravallese’s research focuses on study of the pathogenesis of rheumatoid arthritis, with particular interest in the fundamental mechanisms of bone and cartilage destruction.

Photos courtesy Dr. Ellen Gravallese

According to Dr. Michael Weinblatt, her longtime colleague, "Her research has changed our understanding of the disease, leading to a rethinking of the interaction of inflammation and erosion.

"Some of the erosive process in RA may not all be due to inflammation. It also results from the effect of osteoclasts on bone. The insight that treatment can reduce erosion even when it does not [affect] inflammation may lead to treatment advances," said Dr. Weinblatt, who is the John R. and Eileen K. Riedman professor of medicine at Harvard Medical School, Boston.

Specifically, research done in Dr. Gravallese’s lab has "definitively identified osteoclasts as the cell type responsible for bone destruction in RA, and RANKL as a critical cytokine produced by RA synovial tissues that drive osteoclastogenesis. Anti-RANKL antibodies, recently approved for clinical use, have already been shown to be effective in the prevention of bone destruction in osteoporosis and cancer," according to some biographic material."

"In addition, however, Dr. Gravallese is well known as an outstanding clinician and teacher. Physician-scientists who teach, see patients, and do research are often referred to as ‘triple threats,’ according to Dr. Robert W. Finberg, who was among those who recruited her to the University of Massachusetts 6 years ago.

Indeed, Dr. Gravallese is known to her colleagues as a triple threat plus a little something extra, "Ellen came highly recommended as a creative scientist who had made major discoveries in the area of bone research and the pathogenesis of joint destruction as a result of rheumatoid arthritis. She is internationally known for her contributions to the field of rheumatology," he said. Dr. Gravallese’s achievements prompted one of her colleagues to refer to her as a ‘quadruple threat,’ with expertise in research, clinical medicine, teaching, and service to her profession," said Dr. Finberg, who is chair of the department of medicine at University of Massachusetts where Dr. Gravallese is also professor of medicine and cell biology.

Dr. Gravallese began to test the waters and to challenge the status quo in the patriarchal education system when she was a young student, according to Dr. Katherine Upchurch.

"While in the eighth grade, she sought to single-handedly overturn single-sex education at the then all-male Phillips Academy, in Andover, Mass., where her brothers had gone. She met with the director of admissions at PA to advocate for herself, but it was not to be. I surmise that this may be her only academic failure to date," Dr. Upchurch told an audience the night that Dr. Gravallese won the Marion Ropes Physician Achievement Award from the Arthritis Foundation in 2011.

Dr. Gravallese, the daughter and sister of physicians, was not thinking about a career in rheumatology, much less leading research that may change the management of RA, when she was in medical school. "While in my fourth year of medical school, I had the opportunity to spend a 1-month rotation in Cooperstown, N.Y., at the Mary Imogene Bassett Hospital, which is a community hospital closely associated with Columbia University, N.Y. I had only 1 month open in my schedule for a rotation there, and because I signed up late, there was only one rotation available, which was rheumatology. I must admit it was not my top choice at the time for a clinical rotation."

On such matters of chance an entire professional life can be based.

"However, I was fortunate to work with Dr. Gary Hoffman, who at that time was a young rheumatologist in community practice. I worked side by side with Dr. Hoffman for the entire month, and was fascinated by the patients I saw and was struck by the fact that so little was known about the pathogenesis of their diseases. Dr. Hoffman was such an inspiring mentor," she said in an interview.

Despite that early and rewarding exposure to rheumatology, Dr. Gravallese chose pathology as her specialty. In pathology, "there was a deep understanding of pathophysiologic disease mechanisms, and I felt that this was the area in which I might make the greatest impact in studying disease at the basic level. I first did an internship in internal medicine for 1 year at the Brigham and Women’s Hospital in Boston. Once I moved to pathology, I found that there was a keen appreciation for disease mechanism and a huge opportunity for basic investigation into disease mechanism."

But an unmet need for contact with patients continued to pique her. "I desperately missed the contact with patients and the ability to interact closely with other physicians in the treatment of these patients." After her internal medicine internship from 1981 to 1982 at Brigham and Women’s Hospital in Boston, she undertook a residency in pathology from 1982 to 1984, where she worked with Dr. Joseph Corson, among others. The chief of surgical pathology, Dr. Corson had a special interest in "in the pathologic changes that occurred in the synovium in the rheumatic diseases and had been collecting interesting cases of synovial pathology for his entire career. I was able to work with him in a one-on-one fashion for several months, studying these cases and coming to an understanding of what was and what was not known about the pathogenesis of rheumatic diseases involving the synovium." This was the "eureka" moment that led her to choose rheumatology. From 1984 to 1986, she did 2 more years of internal medicine residency, followed by a rheumatology/immunology fellowship from 1986 to 1988 also at Brigham and Women’s.

Dr. Mittie K. Doyle, a researcher in Dr. Gravallese’s lab in 1994-1996 at the Harvard School of Public Health, also in Boston, noted that her long-time mentor "is actually triple boarded in pathology, internal medicine, and rheumatology."

Dr. Doyle noted that while she worked in Dr. Gravallese’s lab at the Harvard, the focus of her research was a "murine model of Lyme carditis.

"She has made major scientific contributions to the field of rheumatology, specifically in her pursuit to understand the pathogenesis of bone erosion and remodeling in inflammatory arthritis. Along the way, she continues to find the time to mentor young medical students, graduate students, and fellows," said Dr. Doyle, who is director of clinical development in immunology at Johnson & Johnson in Spring House, Penn.

"We met in 1993, when I began my rheumatology fellowship at the Brigham. I was immediately impressed by her superior clinical skills, particularly given her dedication to her innovative basic laboratory work. Ellen’s background in pathology, combined with her clinical expertise, makes her a quintessential translational medicine scientist," Dr. Doyle noted.

But wait, there is another side to Dr. Gravallese. With her husband, Dr. M. Timothy Hresko, she has raised two sons of whom she is immensely proud.

To her young mentors who sometimes lived with Dr. Gravallese’s family while between apartments, the business of parenting while maintaining a cutting-edge research career may have looked easy. But it was not.

"My husband had just left on a trip to a European meeting ... very early the next morning my older son, who was about 7 at the time, woke up short of breath and announced that he was ‘having a heart attack.’ It was croup, and I had to take him urgently to the ER. He was treated, and when we arrived home, I found that our hot-water heater had burst and flooded the basement and our power was out. Just as I had arranged for all of the repairs, my younger son also developed croup."

She survived such back-to-back challenges on the home front with aplomb, even though Dr. Gravallese would be the last person to say so.

Perhaps it is the knowledge that she has survived domestic catastrophes that gave her the pluck needed for her current administrative duties.

Dr. Weinblatt called Dr. Gravallese someone who "remains optimistic about the future of academic medicine." Perhaps, it was that optimism that motivated her to become chief of the rheumatology division at UMass Medical School in 2006, which increased the demands of administration on her time. Since moving to her duties as the chief of rheumatology, "I now focus on the administration of the division but continue to spend much of my time in basic and translational research efforts in RA and bone, and in the study and treatment of patients with rheumatoid arthritis. I see patients with our rheumatology fellows and am involved in the training of medical students, graduate students, and postdoctoral fellows in multiple venues."

Dr. Gravallese has touched the lives and careers of many young rheumatologists in training and they still recall the experience as being fundamental to shaping their lives.

The guys in her family have done more than prepare her for departmental uproar. They have opened her eyes to a pleasure she had been unaware of, at least in a meaningful way, even though she spent most of her life in the greater Boston area. These days, "I am indeed a Red Sox fan. Before I had my two boys I paid no attention to sports. But, as the years went on, I found that the more I heard about baseball from them, the more fascinating it became. Both of my boys are avid sports fans, as is my husband – and all three played baseball."

And speaking of sports metaphors, Dr. Upchurch, clinical chief in her UMass lab, noted that as the result of one of Dr. Gravallese’s innovations in the 6 years since she became rheumatology chief, "We were the first departmental division to develop and implement a scorecard devoted to productivity and quality.

"Our annual outpatient visits are projected to number over 14,000 this fiscal year, a staggering 96% increase, compared with 2006. ... And perhaps most important to us, we consistently are among the top performers in the systemwide Press Ganey patient satisfaction survey. We are where we are in large part because of Dr. Gravallese’s leadership.

"Additionally, she has established a growing clinical research program in our Center, through the recruitment of Dr. Jon Kay, its director. The program now has two dedicated research associates who oversee a growing number of active clinical research projects. Finally, through her leadership and that of Dr. Nancy Liu, our fellowship program director, our fellowship has received a 5-year unconditional accreditation from the Accreditation Council for Graduate Medical Education and receives a record and increasing number of outstanding applications each year," according to Dr. Upchurch. Dr. Lisa Criscione-Schreiber, rheumatology training program director at Duke University, Durham, N.C., was second-year medical student when she applied for an immunology research project in Boston. She joined Dr. Gravallese’s lab for 15 months. "I never would have become a rheumatologist were it not for Ellen. In her lab, I worked with a lupus mouse model, and then she encouraged me to attend some of the rheumatology fellows’ clinical case conferences, which were fascinating and led me to consider a career in rheumatology. Throughout my career, I’ve consulted with her on many matters regarding my career’s trajectory."

One of Dr. Gravallese’s current researchers at the UMass, cell biology doctoral candidate Melissa Matzelle, said that Dr. Gravallese respects her students’ autonomy. "Unlike other principal investigators, who often force a student to work on a narrow project, Ellen has given me the freedom to pursue my passions and interests in my research, often taking my work in new directions.

"She is also cognizant of the importance of a strong professional network for the advancement of my career. While many PIs give their students the opportunity to present research at national and international forums, she has not only done that, but also has gone above and beyond and made a concerted effort to introduce me to many other leading rheumatologists. These new relationships have allowed me to initiate novel collaborative projects."

Ms. Matzelle reported one other aspect of her mentor’s character that impressed her: "I had the opportunity to meet a husband and wife who had both been patients of Ellen’s in the past. They spoke at length about how she worked tirelessly to diagnose and treat their conditions. They raved at how dedicated she was with their care and how she had made the extra effort where other doctors had not."

One of the greatest challenges facing rheumatology is the very nature of the specialty, Dr. Gravallese said. "We are an ‘evaluation and management’ specialty and as such, our revenues are low, compared with more procedural-based specialties. This puts us at a disadvantage in academic centers where resources for divisional growth are limited. It requires some ingenuity and hard work to develop new programs and to continue with innovation. The administrative work that I have done as division chief has opened my eyes to some of the challenges facing academic rheumatology that will be important to solve going forward." But, even with those challenges in mind, Dr. Gravallese said she would do it all over again, with "no regrets."

Dr. Gravallese has served the American College of Rheumatology in multiple capacities, including as chair of the publications committee and a member of the ACR Board of Directors and the ACR Research and Education Foundation Board of Directors. She has made numerous contributions to the rheumatology literature both an as author and member of the editorial advisory boards of Arthritis and Rheumatism, Current Opinion in Rheumatology, and Annals of the Rheumatic Diseases.

The titles on Dr. Gravallese’s bedside table give a clue to her personal taste in reading:"The Innovators Prescription" by Clayton M. Christensen; "The Paris Wife" by Paula McLain; and "The Lost Symbol," Dan Brown’s most recent novel.

Dr. Ellen M. Gravallese has had a trail-blazing and award-winning career in which she has straddled rheumatology to make contributions both to the bench and the bedside. Her accomplishments owe much to her joint abilities to focus on basic research that bears fruit in the form of meaningful clinical improvements in patient management and to foster the next generation of rheumatology investigators. But there has also been a place for serendipity in her trajectory.

As director for translational research at the Musculoskeletal Center of Excellence, University of Massachusetts Memorial Medical Center, Worcester, Dr. Gravallese’s research focuses on study of the pathogenesis of rheumatoid arthritis, with particular interest in the fundamental mechanisms of bone and cartilage destruction.

Photos courtesy Dr. Ellen Gravallese

According to Dr. Michael Weinblatt, her longtime colleague, "Her research has changed our understanding of the disease, leading to a rethinking of the interaction of inflammation and erosion.

"Some of the erosive process in RA may not all be due to inflammation. It also results from the effect of osteoclasts on bone. The insight that treatment can reduce erosion even when it does not [affect] inflammation may lead to treatment advances," said Dr. Weinblatt, who is the John R. and Eileen K. Riedman professor of medicine at Harvard Medical School, Boston.

Specifically, research done in Dr. Gravallese’s lab has "definitively identified osteoclasts as the cell type responsible for bone destruction in RA, and RANKL as a critical cytokine produced by RA synovial tissues that drive osteoclastogenesis. Anti-RANKL antibodies, recently approved for clinical use, have already been shown to be effective in the prevention of bone destruction in osteoporosis and cancer," according to some biographic material."

"In addition, however, Dr. Gravallese is well known as an outstanding clinician and teacher. Physician-scientists who teach, see patients, and do research are often referred to as ‘triple threats,’ according to Dr. Robert W. Finberg, who was among those who recruited her to the University of Massachusetts 6 years ago.

Indeed, Dr. Gravallese is known to her colleagues as a triple threat plus a little something extra, "Ellen came highly recommended as a creative scientist who had made major discoveries in the area of bone research and the pathogenesis of joint destruction as a result of rheumatoid arthritis. She is internationally known for her contributions to the field of rheumatology," he said. Dr. Gravallese’s achievements prompted one of her colleagues to refer to her as a ‘quadruple threat,’ with expertise in research, clinical medicine, teaching, and service to her profession," said Dr. Finberg, who is chair of the department of medicine at University of Massachusetts where Dr. Gravallese is also professor of medicine and cell biology.

Dr. Gravallese began to test the waters and to challenge the status quo in the patriarchal education system when she was a young student, according to Dr. Katherine Upchurch.

"While in the eighth grade, she sought to single-handedly overturn single-sex education at the then all-male Phillips Academy, in Andover, Mass., where her brothers had gone. She met with the director of admissions at PA to advocate for herself, but it was not to be. I surmise that this may be her only academic failure to date," Dr. Upchurch told an audience the night that Dr. Gravallese won the Marion Ropes Physician Achievement Award from the Arthritis Foundation in 2011.

Dr. Gravallese, the daughter and sister of physicians, was not thinking about a career in rheumatology, much less leading research that may change the management of RA, when she was in medical school. "While in my fourth year of medical school, I had the opportunity to spend a 1-month rotation in Cooperstown, N.Y., at the Mary Imogene Bassett Hospital, which is a community hospital closely associated with Columbia University, N.Y. I had only 1 month open in my schedule for a rotation there, and because I signed up late, there was only one rotation available, which was rheumatology. I must admit it was not my top choice at the time for a clinical rotation."

On such matters of chance an entire professional life can be based.

"However, I was fortunate to work with Dr. Gary Hoffman, who at that time was a young rheumatologist in community practice. I worked side by side with Dr. Hoffman for the entire month, and was fascinated by the patients I saw and was struck by the fact that so little was known about the pathogenesis of their diseases. Dr. Hoffman was such an inspiring mentor," she said in an interview.

Despite that early and rewarding exposure to rheumatology, Dr. Gravallese chose pathology as her specialty. In pathology, "there was a deep understanding of pathophysiologic disease mechanisms, and I felt that this was the area in which I might make the greatest impact in studying disease at the basic level. I first did an internship in internal medicine for 1 year at the Brigham and Women’s Hospital in Boston. Once I moved to pathology, I found that there was a keen appreciation for disease mechanism and a huge opportunity for basic investigation into disease mechanism."

But an unmet need for contact with patients continued to pique her. "I desperately missed the contact with patients and the ability to interact closely with other physicians in the treatment of these patients." After her internal medicine internship from 1981 to 1982 at Brigham and Women’s Hospital in Boston, she undertook a residency in pathology from 1982 to 1984, where she worked with Dr. Joseph Corson, among others. The chief of surgical pathology, Dr. Corson had a special interest in "in the pathologic changes that occurred in the synovium in the rheumatic diseases and had been collecting interesting cases of synovial pathology for his entire career. I was able to work with him in a one-on-one fashion for several months, studying these cases and coming to an understanding of what was and what was not known about the pathogenesis of rheumatic diseases involving the synovium." This was the "eureka" moment that led her to choose rheumatology. From 1984 to 1986, she did 2 more years of internal medicine residency, followed by a rheumatology/immunology fellowship from 1986 to 1988 also at Brigham and Women’s.

Dr. Mittie K. Doyle, a researcher in Dr. Gravallese’s lab in 1994-1996 at the Harvard School of Public Health, also in Boston, noted that her long-time mentor "is actually triple boarded in pathology, internal medicine, and rheumatology."

Dr. Doyle noted that while she worked in Dr. Gravallese’s lab at the Harvard, the focus of her research was a "murine model of Lyme carditis.

"She has made major scientific contributions to the field of rheumatology, specifically in her pursuit to understand the pathogenesis of bone erosion and remodeling in inflammatory arthritis. Along the way, she continues to find the time to mentor young medical students, graduate students, and fellows," said Dr. Doyle, who is director of clinical development in immunology at Johnson & Johnson in Spring House, Penn.

"We met in 1993, when I began my rheumatology fellowship at the Brigham. I was immediately impressed by her superior clinical skills, particularly given her dedication to her innovative basic laboratory work. Ellen’s background in pathology, combined with her clinical expertise, makes her a quintessential translational medicine scientist," Dr. Doyle noted.

But wait, there is another side to Dr. Gravallese. With her husband, Dr. M. Timothy Hresko, she has raised two sons of whom she is immensely proud.

To her young mentors who sometimes lived with Dr. Gravallese’s family while between apartments, the business of parenting while maintaining a cutting-edge research career may have looked easy. But it was not.

"My husband had just left on a trip to a European meeting ... very early the next morning my older son, who was about 7 at the time, woke up short of breath and announced that he was ‘having a heart attack.’ It was croup, and I had to take him urgently to the ER. He was treated, and when we arrived home, I found that our hot-water heater had burst and flooded the basement and our power was out. Just as I had arranged for all of the repairs, my younger son also developed croup."

She survived such back-to-back challenges on the home front with aplomb, even though Dr. Gravallese would be the last person to say so.

Perhaps it is the knowledge that she has survived domestic catastrophes that gave her the pluck needed for her current administrative duties.

Dr. Weinblatt called Dr. Gravallese someone who "remains optimistic about the future of academic medicine." Perhaps, it was that optimism that motivated her to become chief of the rheumatology division at UMass Medical School in 2006, which increased the demands of administration on her time. Since moving to her duties as the chief of rheumatology, "I now focus on the administration of the division but continue to spend much of my time in basic and translational research efforts in RA and bone, and in the study and treatment of patients with rheumatoid arthritis. I see patients with our rheumatology fellows and am involved in the training of medical students, graduate students, and postdoctoral fellows in multiple venues."

Dr. Gravallese has touched the lives and careers of many young rheumatologists in training and they still recall the experience as being fundamental to shaping their lives.

The guys in her family have done more than prepare her for departmental uproar. They have opened her eyes to a pleasure she had been unaware of, at least in a meaningful way, even though she spent most of her life in the greater Boston area. These days, "I am indeed a Red Sox fan. Before I had my two boys I paid no attention to sports. But, as the years went on, I found that the more I heard about baseball from them, the more fascinating it became. Both of my boys are avid sports fans, as is my husband – and all three played baseball."

And speaking of sports metaphors, Dr. Upchurch, clinical chief in her UMass lab, noted that as the result of one of Dr. Gravallese’s innovations in the 6 years since she became rheumatology chief, "We were the first departmental division to develop and implement a scorecard devoted to productivity and quality.

"Our annual outpatient visits are projected to number over 14,000 this fiscal year, a staggering 96% increase, compared with 2006. ... And perhaps most important to us, we consistently are among the top performers in the systemwide Press Ganey patient satisfaction survey. We are where we are in large part because of Dr. Gravallese’s leadership.

"Additionally, she has established a growing clinical research program in our Center, through the recruitment of Dr. Jon Kay, its director. The program now has two dedicated research associates who oversee a growing number of active clinical research projects. Finally, through her leadership and that of Dr. Nancy Liu, our fellowship program director, our fellowship has received a 5-year unconditional accreditation from the Accreditation Council for Graduate Medical Education and receives a record and increasing number of outstanding applications each year," according to Dr. Upchurch. Dr. Lisa Criscione-Schreiber, rheumatology training program director at Duke University, Durham, N.C., was second-year medical student when she applied for an immunology research project in Boston. She joined Dr. Gravallese’s lab for 15 months. "I never would have become a rheumatologist were it not for Ellen. In her lab, I worked with a lupus mouse model, and then she encouraged me to attend some of the rheumatology fellows’ clinical case conferences, which were fascinating and led me to consider a career in rheumatology. Throughout my career, I’ve consulted with her on many matters regarding my career’s trajectory."

One of Dr. Gravallese’s current researchers at the UMass, cell biology doctoral candidate Melissa Matzelle, said that Dr. Gravallese respects her students’ autonomy. "Unlike other principal investigators, who often force a student to work on a narrow project, Ellen has given me the freedom to pursue my passions and interests in my research, often taking my work in new directions.

"She is also cognizant of the importance of a strong professional network for the advancement of my career. While many PIs give their students the opportunity to present research at national and international forums, she has not only done that, but also has gone above and beyond and made a concerted effort to introduce me to many other leading rheumatologists. These new relationships have allowed me to initiate novel collaborative projects."

Ms. Matzelle reported one other aspect of her mentor’s character that impressed her: "I had the opportunity to meet a husband and wife who had both been patients of Ellen’s in the past. They spoke at length about how she worked tirelessly to diagnose and treat their conditions. They raved at how dedicated she was with their care and how she had made the extra effort where other doctors had not."

One of the greatest challenges facing rheumatology is the very nature of the specialty, Dr. Gravallese said. "We are an ‘evaluation and management’ specialty and as such, our revenues are low, compared with more procedural-based specialties. This puts us at a disadvantage in academic centers where resources for divisional growth are limited. It requires some ingenuity and hard work to develop new programs and to continue with innovation. The administrative work that I have done as division chief has opened my eyes to some of the challenges facing academic rheumatology that will be important to solve going forward." But, even with those challenges in mind, Dr. Gravallese said she would do it all over again, with "no regrets."

Dr. Gravallese has served the American College of Rheumatology in multiple capacities, including as chair of the publications committee and a member of the ACR Board of Directors and the ACR Research and Education Foundation Board of Directors. She has made numerous contributions to the rheumatology literature both an as author and member of the editorial advisory boards of Arthritis and Rheumatism, Current Opinion in Rheumatology, and Annals of the Rheumatic Diseases.

The titles on Dr. Gravallese’s bedside table give a clue to her personal taste in reading:"The Innovators Prescription" by Clayton M. Christensen; "The Paris Wife" by Paula McLain; and "The Lost Symbol," Dan Brown’s most recent novel.

Dr. Ellen M. Gravallese has had a trail-blazing and award-winning career in which she has straddled rheumatology to make contributions both to the bench and the bedside. Her accomplishments owe much to her joint abilities to focus on basic research that bears fruit in the form of meaningful clinical improvements in patient management and to foster the next generation of rheumatology investigators. But there has also been a place for serendipity in her trajectory.

As director for translational research at the Musculoskeletal Center of Excellence, University of Massachusetts Memorial Medical Center, Worcester, Dr. Gravallese’s research focuses on study of the pathogenesis of rheumatoid arthritis, with particular interest in the fundamental mechanisms of bone and cartilage destruction.

Photos courtesy Dr. Ellen Gravallese

According to Dr. Michael Weinblatt, her longtime colleague, "Her research has changed our understanding of the disease, leading to a rethinking of the interaction of inflammation and erosion.

"Some of the erosive process in RA may not all be due to inflammation. It also results from the effect of osteoclasts on bone. The insight that treatment can reduce erosion even when it does not [affect] inflammation may lead to treatment advances," said Dr. Weinblatt, who is the John R. and Eileen K. Riedman professor of medicine at Harvard Medical School, Boston.

Specifically, research done in Dr. Gravallese’s lab has "definitively identified osteoclasts as the cell type responsible for bone destruction in RA, and RANKL as a critical cytokine produced by RA synovial tissues that drive osteoclastogenesis. Anti-RANKL antibodies, recently approved for clinical use, have already been shown to be effective in the prevention of bone destruction in osteoporosis and cancer," according to some biographic material."

"In addition, however, Dr. Gravallese is well known as an outstanding clinician and teacher. Physician-scientists who teach, see patients, and do research are often referred to as ‘triple threats,’ according to Dr. Robert W. Finberg, who was among those who recruited her to the University of Massachusetts 6 years ago.

Indeed, Dr. Gravallese is known to her colleagues as a triple threat plus a little something extra, "Ellen came highly recommended as a creative scientist who had made major discoveries in the area of bone research and the pathogenesis of joint destruction as a result of rheumatoid arthritis. She is internationally known for her contributions to the field of rheumatology," he said. Dr. Gravallese’s achievements prompted one of her colleagues to refer to her as a ‘quadruple threat,’ with expertise in research, clinical medicine, teaching, and service to her profession," said Dr. Finberg, who is chair of the department of medicine at University of Massachusetts where Dr. Gravallese is also professor of medicine and cell biology.

Dr. Gravallese began to test the waters and to challenge the status quo in the patriarchal education system when she was a young student, according to Dr. Katherine Upchurch.

"While in the eighth grade, she sought to single-handedly overturn single-sex education at the then all-male Phillips Academy, in Andover, Mass., where her brothers had gone. She met with the director of admissions at PA to advocate for herself, but it was not to be. I surmise that this may be her only academic failure to date," Dr. Upchurch told an audience the night that Dr. Gravallese won the Marion Ropes Physician Achievement Award from the Arthritis Foundation in 2011.

Dr. Gravallese, the daughter and sister of physicians, was not thinking about a career in rheumatology, much less leading research that may change the management of RA, when she was in medical school. "While in my fourth year of medical school, I had the opportunity to spend a 1-month rotation in Cooperstown, N.Y., at the Mary Imogene Bassett Hospital, which is a community hospital closely associated with Columbia University, N.Y. I had only 1 month open in my schedule for a rotation there, and because I signed up late, there was only one rotation available, which was rheumatology. I must admit it was not my top choice at the time for a clinical rotation."

On such matters of chance an entire professional life can be based.

"However, I was fortunate to work with Dr. Gary Hoffman, who at that time was a young rheumatologist in community practice. I worked side by side with Dr. Hoffman for the entire month, and was fascinated by the patients I saw and was struck by the fact that so little was known about the pathogenesis of their diseases. Dr. Hoffman was such an inspiring mentor," she said in an interview.

Despite that early and rewarding exposure to rheumatology, Dr. Gravallese chose pathology as her specialty. In pathology, "there was a deep understanding of pathophysiologic disease mechanisms, and I felt that this was the area in which I might make the greatest impact in studying disease at the basic level. I first did an internship in internal medicine for 1 year at the Brigham and Women’s Hospital in Boston. Once I moved to pathology, I found that there was a keen appreciation for disease mechanism and a huge opportunity for basic investigation into disease mechanism."

But an unmet need for contact with patients continued to pique her. "I desperately missed the contact with patients and the ability to interact closely with other physicians in the treatment of these patients." After her internal medicine internship from 1981 to 1982 at Brigham and Women’s Hospital in Boston, she undertook a residency in pathology from 1982 to 1984, where she worked with Dr. Joseph Corson, among others. The chief of surgical pathology, Dr. Corson had a special interest in "in the pathologic changes that occurred in the synovium in the rheumatic diseases and had been collecting interesting cases of synovial pathology for his entire career. I was able to work with him in a one-on-one fashion for several months, studying these cases and coming to an understanding of what was and what was not known about the pathogenesis of rheumatic diseases involving the synovium." This was the "eureka" moment that led her to choose rheumatology. From 1984 to 1986, she did 2 more years of internal medicine residency, followed by a rheumatology/immunology fellowship from 1986 to 1988 also at Brigham and Women’s.

Dr. Mittie K. Doyle, a researcher in Dr. Gravallese’s lab in 1994-1996 at the Harvard School of Public Health, also in Boston, noted that her long-time mentor "is actually triple boarded in pathology, internal medicine, and rheumatology."

Dr. Doyle noted that while she worked in Dr. Gravallese’s lab at the Harvard, the focus of her research was a "murine model of Lyme carditis.

"She has made major scientific contributions to the field of rheumatology, specifically in her pursuit to understand the pathogenesis of bone erosion and remodeling in inflammatory arthritis. Along the way, she continues to find the time to mentor young medical students, graduate students, and fellows," said Dr. Doyle, who is director of clinical development in immunology at Johnson & Johnson in Spring House, Penn.

"We met in 1993, when I began my rheumatology fellowship at the Brigham. I was immediately impressed by her superior clinical skills, particularly given her dedication to her innovative basic laboratory work. Ellen’s background in pathology, combined with her clinical expertise, makes her a quintessential translational medicine scientist," Dr. Doyle noted.

But wait, there is another side to Dr. Gravallese. With her husband, Dr. M. Timothy Hresko, she has raised two sons of whom she is immensely proud.

To her young mentors who sometimes lived with Dr. Gravallese’s family while between apartments, the business of parenting while maintaining a cutting-edge research career may have looked easy. But it was not.

"My husband had just left on a trip to a European meeting ... very early the next morning my older son, who was about 7 at the time, woke up short of breath and announced that he was ‘having a heart attack.’ It was croup, and I had to take him urgently to the ER. He was treated, and when we arrived home, I found that our hot-water heater had burst and flooded the basement and our power was out. Just as I had arranged for all of the repairs, my younger son also developed croup."

She survived such back-to-back challenges on the home front with aplomb, even though Dr. Gravallese would be the last person to say so.

Perhaps it is the knowledge that she has survived domestic catastrophes that gave her the pluck needed for her current administrative duties.

Dr. Weinblatt called Dr. Gravallese someone who "remains optimistic about the future of academic medicine." Perhaps, it was that optimism that motivated her to become chief of the rheumatology division at UMass Medical School in 2006, which increased the demands of administration on her time. Since moving to her duties as the chief of rheumatology, "I now focus on the administration of the division but continue to spend much of my time in basic and translational research efforts in RA and bone, and in the study and treatment of patients with rheumatoid arthritis. I see patients with our rheumatology fellows and am involved in the training of medical students, graduate students, and postdoctoral fellows in multiple venues."

Dr. Gravallese has touched the lives and careers of many young rheumatologists in training and they still recall the experience as being fundamental to shaping their lives.

The guys in her family have done more than prepare her for departmental uproar. They have opened her eyes to a pleasure she had been unaware of, at least in a meaningful way, even though she spent most of her life in the greater Boston area. These days, "I am indeed a Red Sox fan. Before I had my two boys I paid no attention to sports. But, as the years went on, I found that the more I heard about baseball from them, the more fascinating it became. Both of my boys are avid sports fans, as is my husband – and all three played baseball."

And speaking of sports metaphors, Dr. Upchurch, clinical chief in her UMass lab, noted that as the result of one of Dr. Gravallese’s innovations in the 6 years since she became rheumatology chief, "We were the first departmental division to develop and implement a scorecard devoted to productivity and quality.

"Our annual outpatient visits are projected to number over 14,000 this fiscal year, a staggering 96% increase, compared with 2006. ... And perhaps most important to us, we consistently are among the top performers in the systemwide Press Ganey patient satisfaction survey. We are where we are in large part because of Dr. Gravallese’s leadership.

"Additionally, she has established a growing clinical research program in our Center, through the recruitment of Dr. Jon Kay, its director. The program now has two dedicated research associates who oversee a growing number of active clinical research projects. Finally, through her leadership and that of Dr. Nancy Liu, our fellowship program director, our fellowship has received a 5-year unconditional accreditation from the Accreditation Council for Graduate Medical Education and receives a record and increasing number of outstanding applications each year," according to Dr. Upchurch. Dr. Lisa Criscione-Schreiber, rheumatology training program director at Duke University, Durham, N.C., was second-year medical student when she applied for an immunology research project in Boston. She joined Dr. Gravallese’s lab for 15 months. "I never would have become a rheumatologist were it not for Ellen. In her lab, I worked with a lupus mouse model, and then she encouraged me to attend some of the rheumatology fellows’ clinical case conferences, which were fascinating and led me to consider a career in rheumatology. Throughout my career, I’ve consulted with her on many matters regarding my career’s trajectory."

One of Dr. Gravallese’s current researchers at the UMass, cell biology doctoral candidate Melissa Matzelle, said that Dr. Gravallese respects her students’ autonomy. "Unlike other principal investigators, who often force a student to work on a narrow project, Ellen has given me the freedom to pursue my passions and interests in my research, often taking my work in new directions.

"She is also cognizant of the importance of a strong professional network for the advancement of my career. While many PIs give their students the opportunity to present research at national and international forums, she has not only done that, but also has gone above and beyond and made a concerted effort to introduce me to many other leading rheumatologists. These new relationships have allowed me to initiate novel collaborative projects."

Ms. Matzelle reported one other aspect of her mentor’s character that impressed her: "I had the opportunity to meet a husband and wife who had both been patients of Ellen’s in the past. They spoke at length about how she worked tirelessly to diagnose and treat their conditions. They raved at how dedicated she was with their care and how she had made the extra effort where other doctors had not."

One of the greatest challenges facing rheumatology is the very nature of the specialty, Dr. Gravallese said. "We are an ‘evaluation and management’ specialty and as such, our revenues are low, compared with more procedural-based specialties. This puts us at a disadvantage in academic centers where resources for divisional growth are limited. It requires some ingenuity and hard work to develop new programs and to continue with innovation. The administrative work that I have done as division chief has opened my eyes to some of the challenges facing academic rheumatology that will be important to solve going forward." But, even with those challenges in mind, Dr. Gravallese said she would do it all over again, with "no regrets."

Dr. Gravallese has served the American College of Rheumatology in multiple capacities, including as chair of the publications committee and a member of the ACR Board of Directors and the ACR Research and Education Foundation Board of Directors. She has made numerous contributions to the rheumatology literature both an as author and member of the editorial advisory boards of Arthritis and Rheumatism, Current Opinion in Rheumatology, and Annals of the Rheumatic Diseases.

The titles on Dr. Gravallese’s bedside table give a clue to her personal taste in reading:"The Innovators Prescription" by Clayton M. Christensen; "The Paris Wife" by Paula McLain; and "The Lost Symbol," Dan Brown’s most recent novel.