In Memory of Michael Steven Denison

By Pamela Lein posted 06-30-2022 13:25

Co-authored with Craig Marcus and Stephen "Steve" Safe

Michael S. Denison

Distinguished Emeritus Professor Michael “Mike” Steven Denison of Woodland, California, passed away on March 22, 2022, at age 67. His cause of death was glioblastoma. Mike and his twin brother, Steven, were born on December 8, 1954, in Shirley, Massachusetts, the son of Alan (deceased) and Alma Denison. During his early life, Mike and his family lived in numerous places around the world while his father served in the Army. The family settled in Wharton, New Jersey, when Mike was 11 years old.

Mike received his AA in biology from County College of Morris, Dover, New Jersey; his BS in marine biology from St. Francis College, Biddeford, Maine; his MS in animal physiology from Mississippi State University, Starkville, Mississippi; and his doctorate in environmental toxicology from Cornell University, Ithaca, New York, in 1983. Mike completed two postdoctoral fellowships: the first at Hospital for Sick Children in Toronto, Canada, and the second at Stanford University, Stanford, California. He was appointed Assistant Professor in the Department of Biochemistry at Michigan State University, East Lansing, Michigan, and then relocated to the Department of Environmental Toxicology at University of California Davis (UC Davis), Davis, California, where he was promoted to Professor in 1997.

Mike was a leader in the study of Ah receptor biology and made seminal contributions to our understanding of the molecular mechanisms by which the Ah receptor mediates the biological/toxicological actions of dioxins and related chemicals. He was widely acclaimed for developing the Chemical Activated LUciferase gene eXpression (CALUX) assay, a cell-based bioassay used for the detection of specific environmental contaminants, including dioxin-like chemicals and environmental hormones (endocrine disruptors). This test was approved as an international standard for detecting environmental contaminants by the Organization of Economic Cooperation and Development and by the US Environmental Protection Agency and is internationally utilized to protect human health.

Mike was a happy and optimistic person, who could not resist practical jokes, Hawaiian shirts, brightly colored sneakers, and cooking for family and friends. The few things that he took seriously were science; his commitment to his wife, Grace; his various canine companions across the years; and his friends and students. His typical day was spent at work, conducting research and mentoring students, returning home to make a wonderful dinner for his wife, and then retreating to his home office to work until the wee hours of the following morning. He maintained curiosity and wonder of the world around him and loved to solve problems and figure out how things worked. He was generous with his friends and colleagues alike and always quick to offer his services to those in need.

There will be a celebration of life for Mike on Friday, July 15, 2022, at 4:00 pm on the UC Davis campus. If you cannot attend in person, you are invited to join the event via Zoom.

Donations in memory of Mike may be made to Yolo Cares online or by calling 530.758.5566. Donations also may be made to the Michael S. Denison, Ph.D. ’83 Environmental Toxicology Research Fund, an endowment created at Cornell University by a colleague in Mike’s honor. A check payable to Cornell University may be mailed to Cornell University, Box 37334, Boone, IA 50037-0334. In the memo field or in the correspondence with the check, please notate Michael S. Denison, Ph.D. ’83 Environmental Toxicology Research Fund #0018594. A gift also may be made online by notating Michael S. Denison, Ph.D. ’83 Environmental Toxicology Research Fund #0018594 on the online giving form. Christy Agnese at Cornell University may be contacted at 607.279.6884 for further assistance.

Here are personal tributes from some of the many colleagues who were lucky enough to count Mike as a friend.

By Robert “Bob” Rice, UC Davis, environmental toxicology, excerpted from the presentation that Bob gave at Mike’s retirement from UC Davis

It is my pleasure to share some reflections on Mike’s contributions to the department and the world of science. Since retirement is a happy period to do all those things one never had time for before, I thought I would concentrate on relating a few humorous episodes. However, despite my best efforts, I could not think of any. Of the faculty I consulted, no one else could think of any either. We reluctantly concluded that Mike has never done anything humorous. This really torpedoed my plan for these remarks. After pondering at length, I realized I would have to just summarize a few highlights of Mike’s brilliant career.

Let’s consider teaching. This could arguably be considered our most important function since we and the university are here because of the students. A fundamental principle of toxicology is that the dose makes the poison. This principle was illustrated beautifully each year in Mike’s course ETX 101 “Principles of Environmental Toxicology” in a lecture at the beginning of the course. At the start of the dose-response lecture, Mike passed through the audience a large bowl of chocolate candies wrapped in aluminum foil that looked remarkably like Hershey’s kisses. Many students politely took one piece of chocolate. Some boldly took two pieces. The greedy ones took more than two pieces. Some students do not like chocolate and took none. At the end of the lecture, Mike requested that the students write down the number of pieces they had consumed and a quantitative estimate of their degree of feeling ill. Those turning in the data at the end of class would have access to the antidote. We anticipate publication of a report from this experiment on the evolution of resistance in undergraduates through the years, but I understand the study is still under consideration by the IRB … who are unsure whether to try the chocolate themselves.

The faculty recognize that the single most important factor in receiving an excellent student teaching evaluation is the lecture’s or the course’s entertainment value. Mike’s lectures and courses always got excellent evaluations. This propensity to provide entertainment has been a major contribution to his service to the department, campus, and wider scientific community. For example, Mike has given many prestigious keynote addresses over the years at national and international conferences. I recall the final planning for one international address some years ago that involved his identical twin brother, Steve, who was to accompany him to the exotic meeting location. The address concerned the controversial re-evaluation of the risk to the public from exposure to dioxin (TCDD). This included a risk assessment model popular in Europe and led to the question, “Are we safer now than before?” The presentation would consist of a debate between Mike and Steve at the podium with each taking one side of the question. It was required that each must consider the opinion and position of the other in their response, and the response must be strongly supported by well-documented scientific results and conclusions. Mike started the debate with an emphatic, “Yes, we are safer,” and Steve responded with a robust, “No, we are not,” and you can imagine how this went: “Yes, we are”; “No, we’re not”; “Yes, we are”; “No, we’re not,” until the time limit was reached. I did not learn whether they were ever invited to repeat the lecture at other such conferences.

As you can see, Mike and Steve are theoretically an effective tag team. Another plan (well before the current merit/promotion system was introduced) was for Steve to walk into the office of the department Chair, Marion Miller, and demand a raise or else he would leave. If she said, “Yes,” that would be great for Mike. If she said, “No,” Steve would then walk out as he had threatened. If Marion asked Mike about it later, he could pin the blame on Steve, who would escape unscathed.

Another example reflects that Mike often had interesting recorded messages for those who called his office when he was absent. The one I remember best sounded exactly like Governor Schwarzenegger, including the Austrian accent, saying he could not come to phone because he was too busy preparing a poison to terminate the girly men who gave bad reviews of his journal manuscripts. The office phone frequently received calls at odd hours, but few callers left messages. One evening, when Mike picked up, the caller expressed regret at disturbing him since he was calling just to listen to the recorded message. A colleague of Mike’s was passing out the phone number to friends.

Now for research. The faculty realize that regardless of our teaching and service exploits, our real legacy consists of the published record of our experiments. Mike has a stellar publication record on activation of the aryl hydrocarbon receptor by dioxin (TCDD) and a myriad of chemicals, even those we encounter in daily life, such as newsprint and rubber stoppers. Less recognized is the research that may perhaps be his most enduring claim to fame: the response of rats to nickel exposure. This work employed rats genetically engineered by the US Treasury Department to have a dorsal monetary access channel (a slot on the back) into which coins could be inserted. As we all know, biotransformation of exogenous compounds is usually a critical determinant of toxic response. Amazingly, the rats biotransformed the inserted nickel into copper (i.e., pennies), and the rats could even generate nickel if a quarter was inserted, producing two dimes in addition. From a PubMed perspective, this publication received one of the highest actual citation rates ever seen for a paper in the Journal of Irreproducible Results—that’s right, one—and it was reprinted in Veterinary and Human Toxicology, garnering a reprint request from a researcher specializing in nickel and cobalt effects on metabolism.

Mike astutely realized he had an opportunity to equal and possibly surpass this success when I showed him an electron micrograph of a terminally differentiated human keratinocyte. The micrograph, showing the dead cell in the exact shape of a shoeprint, was evidence of an unrecognized mechanism of cell death that had previously been misinterpreted as apoptosis. On this basis, the real mechanism was named more accurately as “astomptosis.” Details remain to be elucidated such as the identity of the terminator cells or entities, but the shoe print did match the Bruno Maglis worn by O.J. Simpson. I was grateful to be a co-author, although I insisted on my name being spelled backward. The reviews were positive, but the editor rejected it on the grounds it was too scientific for the Journal of Irreproducible Results. We were devastated since this was a huge impediment to our becoming rich and famous, to receiving a two-step merit increase, and to being considered for the annual Ig Nobel Award. However, we have not given up; there is still the rival journal, Annals of Improbable Research.

Mike Denison (left) and Heidi Fiedler (right)
in Kyoto, Japan, in 2019

By Heidelore “Heidi” Fiedler, Örebro University School of Science and Technology and International Advisory Board (IAB) of the Dioxin Symposia

When Michael S. Denison passed away on 22 March 2022, the scientific community lost a great researcher and many of us a friend. His contributions to elucidate molecular mechanisms to better understand the toxicological actions of dioxin-like compounds and other endocrine-disrupting chemicals made him a world renowned scientist. His legacy with hundreds of papers in peer-reviewed journals will remain.

I met Mike for the first time at Dioxin ‘90 when the conference was held in Bayreuth, Germany, and for the last time at Dioxin 2019 in Kyoto, Japan—none of us imagined that would be the last. For more than 20 years, we jointly served the international advisory board (IAB) of the Dioxin Symposia as Secretaries. The “dioxin community” will remember him as a dear friend and colleague; we will miss his presence and presentations.

We share many memories, such as the annual appearances at the International Dioxin Symposia to award the best student presentations during the closing ceremony of the conference. These little moments showed his passion for science and his love for Hawaiian shirts. May the pleasant and lasting memories help to overcome grief and mourning.

By Linda S. Birnbaum, Scientist Emeritus and Former Director the National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program and Duke University Nicholas School of the Environment Scholar in Residence

Mike Denison was a really unique friend and colleague. Always wearing his Hawaiian shirts, always with a big smile, always with a laugh, and always ready to talk science—or almost anything else.

I got to know Mike from our shared interest in dioxins and the AhR. I still can’t believe some of the studies he did identifying ligands of the AhR—extracts from dirty sneakers is one that I’ll never forget. He also did such elegant studies on the 3D structure with his colleagues in Milan. He had the courage to Chair the international Dioxin meetings in Monterey; it was a great meeting in a wonderful location. And somehow, he got roped into being a deciding official on where following meetings would be. He also played a leading role in the work on the Toxicology Education Foundation approach for dioxin-like compounds. He is already missed!

By Richard “Rick” Pollenz, Professor of science education and Director University of South Florida (USF) SEA PHAGES and USF SEA GENES Programs

I came into the AhR and dioxin field in the early 90s as a postdoc who did not work in this discipline as a graduate student. Thus, I was not connected with the leaders in the field and was finding my way. Mike was immediately approachable and helpful to me with his laid-back California style and colored shirts (no suits and ties!). While others in the field were more guarded, Mike always was willing to share new data and provide reagents and advice. He was a great help to me at the start of my career and leaves an outstanding legacy, not just of his science, but of being a good person who truly cared about others.

By Hollie Swanson, University of Kentucky, former Postdoctoral Fellow of the Mike Denison Laboratory

Mike loved interacting with people and getting groups together. For many years, he would organize dinners and social hours at the SOT Annual Meeting for a group that he sometimes called “The Not So Young Guns.” I’m not quite sure what the eligibility requirements were for that group.

By Gary Perdew, Pennsylvania State University

I first met Mike at an SOT Annual Meeting and found him to be smart, funny, and just an all-around great guy with whom to talk science. We were part of a group called the “Young Guns” at SOT meetings—unfortunately, over the years, our group became “not so young.”

I enjoyed our numerous conversations about the biochemistry of the AhR. Mike made significant unique contributions to the AhR field that really laid the groundwork for its rapid expansion today. He generously gave of his time serving both the fields of toxicology and AhR research.

On a personal note, I once went snow tubing with Mike in State College. He had the grand idea to link tubes together and promptly got in trouble for going too fast and fa, as we sailed over the pine trees set up as a barricade at the bottom of the run. So, he was truly a unique, wonderful, fun-loving, super smart individual, and he will truly be missed!

By Christoph Vogel, UC Davis Department of Environmental Toxicology

Mike was a longtime collaborator, and we were still working together on a grant proposal months before he passed. Mike was an open-minded, hard-working, and passionate researcher who was a great scientist and knew every aspect of dioxins and AhR biology. For me, he was the Francis Crick of the AhR field, describing the crucial role of the AhR complex and its DNA-binding motif for the AhR signaling pathway. It’s not fair that Mike was not able to live long enough to enjoy his time and energy in retirement. He will be greatly missed.

By Pamela “Pam” Lein, UC Davis

It was a considerable privilege for me to put together this tribute to the legacy of Mike Denison. He was a smart, funny, warm, and beloved friend who enriched my life and that of many others. A unique blend of silly and serious, you could rely on him for a laugh when you needed it most, and more importantly, you could count on him to come through when the going got tough. Mike, thank you for being a part of our lives—you will live forever in our hearts and minds.

By Courtney Sulentic, Wright State University Department of Pharmacology and Toxicology

As a graduate student interested in the AhR and the role it might play in B cells, I naturally read Mike’s papers to better understand the AhR and thought of him as one of the AhR gods. Imagine my surprise when I saw him for the first time at an SOT Annual Meeting: he wasn’t scary at all but laid-back in a Hawaiian shirt, jeans, and tennis shoes. I felt much less intimidated to go up to him and introduce myself and ask him questions. Mike made me feel at ease and worthy to talk to. After that first meeting, I made a point of trying to connect with him at future SOT meetings; he was very obliging and always fun to talk to.

Mike was always very generous with his time. I was having difficulty determining if some negative results were valid, and he offered to run an experiment for me, which confirmed our results. Mike also gave me some valuable feedback on one of my papers, and more recently, he met with me virtually to discuss one of my grants, unbeknownst to me before the meeting that he was dealing with his illness. The fact that he would make time to still meet with me and spend a lot of time discussing the aims of my grant, giving me feedback, and even writing a letter of support is humbling. I wish we had more time with him. It is hard knowing that Mike will no longer be seen at meetings in his usual Hawaiian attire and easy manner. He was a pillar in the AhR community, and I am very glad to have known him for the short time that I did.

By Craig Marcus, Oregon State University Department of Environmental and Molecular Toxicology

Mike Denison was internationally known as an accomplished scientist, and his contributions to the understanding of AhR biology are extensive. Mike was a unique scientist in his ability to combine his passion for his science with his enthusiasm for having fun with both his science and in his personal life, as well as sharing both with his colleagues and friends.

I first met Mike in 1981 when I joined the lab of Dr. Chris Wilkinson at Cornell University for my first postdoctoral fellowship. The first day of my fellowship I walked into the lab and was introduced to Mike, who was conducting surgery to remove the midguts of several hundred Spodoptera eridania to isolate cell fractions to study the AhR as one of his projects for his doctoral thesis. Mike’s desk was located next to mine, and over the next two years that we overlapped in the Wilkinson lab, I became very good friends with Mike. For one of those years, we were even roommates, sharing many adventures that often included our dogs, Mike’s greyhound and my beagle.

Mike also was always a leader (and instigator) both in the lab and on campus. I recall how Mike constructed a 20 foot–long vehicle intended to resemble an insect larvae, using truck tire inner tubes and PVC pipe. He then coerced me and several other of his friends to join him on the faux larvae in the annual “anything that floats but is not a boat” race. Mike’s vehicle did make it to the finish line without drowning anyone (barely), and although we didn’t place well, a photo of us on Mike’s entry did end up on the official Cornell Calendar that year (back when calendars were printed on paper). Mike was always the prankster, and I was often the target of his efforts. I never knew what I might find on or in my desk or lab bench, and after one trip to a conference, I returned to the lab to find that I had been summarily replaced by a mannequin sitting at my desk wearing my lab coat. Mike is well known among his friends and colleagues for his constant good nature and humor, and his annual holiday card was always a highlight of the holiday season.

After our time together at Cornell, Mike and I remained in close contact as friends and colleagues. I had the pleasure to serve with Mike on NIEHS study sections and was always impressed with his attention to detail and the breadth of his scientific knowledge—not just limited to the field of AhR receptor biology but to the broader field of toxicology as well. Mike and I were often informal collaborators and consultants on AhR- and CYP-related topics and projects over the past 40 years, and he will be missed intensely by me and many others as a friend and colleague.

By Bruce Hammock, UC Davis Department of Entomology

I wrote elsewhere on the amazing science Mike contributed. His work was the epitome of the NIEHS Superfund Program: serious fundamental biochemistry translated into an assay to monitor the potential of human exposure to superfund chemicals, actual exposure and biological effect on man and the environment. So I will restrain this to a tiny glimpse of Mike Denison.

I had heard of Mike and his antics with Chris Wilkinson at Cornell and again at Michigan State University—there was a period of silence between involving flamingos. Since I was PI of the UC Davis Superfund grant and always trolling for talent, I rushed to meet Mike when he arrived in Davis in fall 2002. He first told me that his wife said she was moving to California, and he could come if he wanted. I had gotten a similar ultimatum in Chicago from my wife, so we started with a lot in common. I soon found that Mike was very serious about his wife, Grace; his science; and not much else—maybe his dog Murphy? So we started meeting a couple of times a week for coffee or lunch at a spot between the two labs. We agreed that Mike would circle the spot in a clockwise direction, and I would go counterclockwise to be sure to meet. So, a third of the time we returned to our labs without coffee because the other person had gone the wrong way.

The science with Mike was always exciting and fun, as were other things that were continually unexpected. For months, pictures of me as a teenager appeared around campus, sometimes with descriptions of ladies I had dated in my teens. It was the dawn of the internet, so I decided someone was finding out about me online. Then, one day, my building was covered with pictures of 15- to 18-year-old Bruce. As one might guess, it was Mike. Sophisticated tricks continued throughout our time together, including a lawn of Christmas trees, a wheelbarrow of bull manure delivered during a lecture, and similar antics. He gave me several lovely gifts, including a model of a motel in the eastern Sierra and a valued piece of sports equipment. He also provided a model of me during renal dialysis that is a bit too incorrect to show but fun nonetheless.

During a year in the hospital, it was Mike and a couple of other colleagues that covered for me with the university. This is the real Mike: a seriously loyal and supportive friend. Additional good fortune was Grace Denison, who administered the NIEHS Superfund Program for years. Grace was afraid of bats, which continually appeared in the office courtesy of her husband. I had high hopes of Mike taking over the Superfund, returning me to important things like kayaking and climbing. Sadly, he retired. But I was lucky in retaining a stimulating, innovative, hilarious, and loyal friend and colleague—and I so miss Mike.

By Paige Lawrence, University of Rochester Department of Environmental Medicine

At some point in the past, Mike and I had, for reasons that I can’t recall, conversations about Clint Eastwood movies. One time, a session that Mike’s talk was in was called “The Ligands: The Good, Bad, and Ugly,” and he titled his talk “A Fistful of Ligands”; I am not sure if anyone other than Mike and I were chuckling about the references, but it amused us. Mike was generous and warm hearted and made me laugh—a lot. I think it is safe to say that he has had a far-reaching positive impact on not only science but on the careers of many scientists.

By Steve Safe, Texas A&M University

To Mike:

Mike Denison and Steve Safe
taking pieces of the Berlin Wall

Mike’s passing was a tragedy felt by his many colleagues and friends.
He was funny but also introspective: a complex mixture with many blends.
Science and the Ah-Receptor were all within his embrace,
But most of all, he loved Grace.

I interacted with Mike at so many meetings, it’s hard to keep a tally.
One of the best was with Grace, Mike, and Pam on a tour of Napa Valley.
In Amsterdam at the Dioxin meeting, Mike took me out for coffee;
there was also tea, some smoke, various pipes, and all kinds of THC.

The 1990 Dioxin meeting in Bayreuth was rich with scientific content.
However, at the end of day two, we felt that our energies were now spent.
Excitement was in the air and the old Soviet Union was in free fall,
we rented a car, headed east to the Czech border, then north to the Berlin Wall.

Presidents, statesmen, Mike, and I stared at the edifice and said with a stammer,
“We need some of that wall. Who has a hammer?”
For 2.5 marks, we pounded and chipped at this stony mystery
and dreamt that we really were witnesses to history.

All of us knew Mike differently but had similar conclusions:
He was both ultra-comical and serious and had few delusions.
I am certain in his way he loved everyone as we all loved him,
and he would no doubt remind us to live our lives to the brim.

Rest in peace, Mike.

Mike Denison speaking
during the
P450/AHR meeting
in Woods Hole

By Mark Hahn, Woods Hole Oceanographic Institution Biology Department

I met Mike at my first SOT Annual Meeting in Boston in 1982 when we were grad students. The following year, he gave a seminar in my department at the University of Rochester Medical School, presenting some of his early work on the comparative biology of the AhR. Mike went on to make major contributions to our understanding of AhR structure and function in several areas, including AhR stability, ligand-binding, transformation, and DRE-binding, while also developing tools that are widely used in the field. However, it was his early (and subsequent) comparative research that influenced my thinking about AhR, raising questions about AhR diversity and evolution that continue to drive much of the research in my lab. I was fortunate to have been able to collaborate with Mike on several projects—most of them dealing with AhR comparative biology—and to have become good friends with him, spending time together in Davis and Woods Hole, in addition to many scientific meetings. One of the latter was a small P450/AHR meeting in Woods Hole in 2007 at which he gave an inspiring keynote address.

Mike was a talented and insightful researcher, a generous colleague and collaborator, and a wonderful person. He was serious—especially about his science—but also silly, irreverent, and unpretentious. By his example, Mike encouraged all to not take ourselves too seriously and to have fun with our work and each other.