Featured Researcher — Steve Goodman, PhDFeatured Researcher — Steve Goodman, PhD https://pediatricsnationwide.org/wp-content/themes/corpus/images/empty/thumbnail.jpg 150 150 Katie Brind'Amour, PhD, MS, CHES Katie Brind'Amour, PhD, MS, CHES https://pediatricsnationwide.org/wp-content/uploads/2021/03/Katie-B-portrait.gif
- December 01, 2021
- Katie Brind'Amour, PhD, MS, CHES
Steven D. Goodman, PhD, is a principal investigator in the Center for Microbial Pathogenesis in the Abigail Wexner Research Institute at Nationwide Children’s Hospital. His research centers on bacterial biofilms — interactive ecosystems of bacteria that form a structure to help the bacteria thrive and fight off threats.
These biofilms can be found wherever bacteria grow, but Dr. Goodman’s lab specializes in the study of oral biofilms, such as the ones that cause dental caries and plaque.
His research investigates how proteins and DNA create extracellular structures that protect bacteria living in biofilms.
By identifying the key elements of these structures and systems, Dr. Goodman hopes to find targets for weakening harmful biofilms so medications or the immune system can effectively remove them. In his latest publication, released in November in Cell, Dr. Goodman and colleagues revealed the presence and role of a previously underrecognized form of DNA (called Z-DNA) in biofilm stabilization — and a potential way to target it to enable biofilm disruption. These findings, coupled with prior collaborative research into the removal of key binding proteins that hold biofilms together, are now at the root of a company that has licensed this potential therapeutic approach: Clarametyx Biosciences. By advancing his research through continued basic science efforts as well as the emerging therapeutic approaches licensed by Clarametyx, Dr. Goodman’s ultimate aim is to help patients with chronic illnesses and infections caused by bacteria in biofilms.
Read on to learn more about Dr. Goodman and his research journey.
Why did you decide to pursue a career in your field?
I always wanted to be a scientist. In college, I majored in both astronomy and biochemistry; I wanted to be an astronaut. As much as I loved astronomy, I found doing biochemical research to be much more satisfying; answers to questions seemed much more attainable.
What was your path to your current role?
Accidental — timing is everything! But I am a firm believer that if you work hard, you will be able to take advantage of opportunities when they come to you.
When I was doing my post-doctoral work at the National Institutes of Health (NIH), I became an expert in how proteins and DNA interact to form biologically relevant structures inside the cell. That area of science was expanding with no end in sight in the late 1980s, and the work I did at the time was considered groundbreaking. But by the time I actually applied for jobs, the field had dried up — no one knew how to move forward, and everyone lost interest in it. I went from being a sort of minor celebrity to someone who couldn’t find a job.
I sent out 90 job applications. As the first batch of rejections came back, I decided I needed to expand my options. My graduate work had been in infectious disease, so some of those 90 applications were for places interested in more general microbiology and infectious disease work. One happened to be for the School of Dentistry at the University of Southern California, which offered me a job. I knew nothing about oral microbiology at all. It was a very steep learning curve for me, and I worked hard to make name for myself in that field.
Even though I didn’t know what biofilms really were at the time, biofilms and oral microbiology go hand in hand. About 90% of oral diseases are biofilm-dependent, both above and below the gumline. I wasn’t at USC long before people started associating me with biofilms, and my colleagues kept telling me that biofilms were “where it’s at.” I felt that biofilms were knocking at my door, and I probably needed to start asking questions and driving my research toward them.
That was 20 years ago, and I haven’t looked back!
Why did you decide to pursue your work at Nationwide Children’s?
I was working as the Chair of Biomedical Sciences at USC and saw coming here would give me many new opportunities to succeed, including the chance to advance my collaborative biofilm research and launch and direct the hospital’s Oral-Gastrointestinal Microbiology Research Affinity Group (OGM RAG).
Nationwide Children’s had research affinity groups, but they wanted to get one started for oral and gastrointestinal (GI) microbiology. Research affinity groups promote more thoughtful and deliberate clinical science that’s truly plugged into what’s going on in the clinic. The cross-fertilization between basic research and clinical science helps overcome the disconnect between what scientists think is important and what clinicians are actually burdened with. The OGM RAG allows people to interact, share data and discuss, promote and critique each other’s work.
At first, the connection between oral and GI microbiology wasn’t obvious to me. But then there was this slow evolution of microbiome sciences. Oral and GI are the two disciplines that promote microbiome science, so that became the connection. Even though some OGM RAG members don’t do microbiome analysis, they’re aware of its importance, and we all learn from one another. It’s a very powerful venue for members.
What is your favorite part of your job?
Discovery! And the latest one we’ve made is a big deal — it’s one of those times when a domino falls, and suddenly you can see connections throughout biology.
It started with one simple question. It was shown about 20 years ago that if you take almost any bacteria and throw them on a surface, they will form a biofilm — a community of bacteria with an extracellular matrix. Everything that was inside the cells typically ends up outside and allows bacteria to protect themselves against their environment. One of those inside-out constituents is DNA.
A colleague asked back then, “If I take an enzyme that degrades DNA and mix it with the bacteria, how will it affect the biofilm?” And it was astonishing: the enzymes prevented biofilms from forming.
There was a flurry of publications after this and everyone was excited. But the problem that emerged was as biofilms matured, those enzymes didn’t work anymore. There was speculation that once the biofilms are established, DNA must not be important, but that idea got under my skin.
Lauren Bakaletz, PhD, director of the Center for Microbial Pathogenesis, and I identified a family of proteins that became more important to forming DNA structures with time, not less. If you pulled those proteins out, the biofilm collapsed. But we still couldn’t figure out how to break mature biofilm DNA down. We went through tons of enzymes that cleave DNA in different ways, and nothing worked.
One day, about four or five years ago, it suddenly hit me that there is one form of DNA that is resistant to enzymes: Z-DNA.
Fun Facts About Dr. Goodman
What fictional character would you most like to meet?
Atticus Finch (To Kill a Mockingbird).
What do you usually eat for breakfast?
What would be your dream job if you could do anything (that wasn’t working in research)?
I would be a shepherd.
A long time ago, I needed help with my rescue dog. I got along fine with her, but her behavior was dangerous. I saw an ad in the LA Times for a dog socializer, and I ended up being one of Cesar Milan’s first clients. He worked his magic and she became much better trained, but he told me she needed a job. A friend told me about a place you could take your dog to train them to herd sheep. My dog took to it instantly, and from that time on, we went sheep-herding every Thursday.
One year, I took a horseback-riding vacation to France and stopped at a breathtaking, perfectly bucolic village. As I was watching the sunset, I heard sheep behind me being driven in by shepherd dogs and I thought to myself, “How hard would it be to give up everything, grab the dog, move to France and do this for a living?” It was one of the most serene moments of my life.
Favorite way to relax?
Favorite thing you’ve bought this year?
A combination coffeemaker, toaster oven and griddle, literally called a 3-in-1. It has become indispensable for RV camping.
It was discovered decades ago and is a weird, zig-zag-shaped left-handed helix. It takes an enormous amount of energy to convert classic DNA to this form and keep it that way, and people didn’t research it much because they didn’t think there were convincing situations in nature where Z-DNA could be stable.
But one researcher, Alexander Rich, MD, dedicated his career to studying Z-DNA and came up with many tests and ways to change normal right-handed DNA into a left-handed helix. Interestingly, he found our own immune systems produce proteins that bind to Z-DNA, and even make antibodies to Z-DNA. We were all scratching our heads: Why would our immune system be looking for Z-DNA? Where is it even found?
That’s where my work spring-boarded from his. As it turns out, as biofilms mature, their DNA gets converted into Z-DNA. Z-DNA is the primary structural component of biofilms, because it is resistant to enzymes that can degrade it. We realized what our innate immune system may have been looking at when it evolved to target Z-DNA: biofilms!
Dr. Rich inadvertently developed all the tools we needed to take his findings and mount a frontal assault on biofilms. Knowing biofilms’ structures rely on Z-DNA means if you can drive the DNA back to its right-handed form, you can get biofilms to fall apart. We also discovered bacteria disable the innate immune system’s efficacy by forming Z-DNA. These are other dominoes that fell: identifying the importance of Z-DNA provided the opportunity to start getting rid of bad biofilms and to better regulate and protect the immune system so it functions properly and not too weakly or too strongly.
I’m grateful I could help connect these dots. These pieces were floating around and puzzling, and we have a possible explanation now. The response to our paper has been very powerful — a lot of “Aha! Of course, there’s the connection!” To us, that’s a very big deal.
How does your research serve our patients and our community?
All of my work drives toward curing people of chronic infections. That’s why we’ve licensed the intellectual property behind this Z-DNA breakdown approach to Clarametyx Biosciences. Once you turn Z-DNA back into regular DNA, you can break down the biofilm structure and kill the bacteria. If they can turn this knowledge into a way to target biofilms, chronic infectious diseases that rely on biofilms could be treated and even cured. It could also help improve the efficacy of existing antibiotics and reduce the risk of bacterial resistance. That could mean amazing things for a lot of people who suffer from these infections.
What’s next? What do you hope to accomplish in your research and professional development going forward?
Our recent fundamental discoveries have knocked down some key dominoes, and more will follow. It’s exciting to be at the forefront as this field opens up. These new discoveries come with strategies and therapeutic candidates that can be tested, and we will be working hard to drive these candidates into the clinic.
Read more about Dr. Goodman’s research:
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