As a physician-scientist, Bruce Bochner, MD, Samuel M. Feinberg Professor in Medicine, investigates the mechanisms behind allergies, asthma, sinusitis and other diseases associated with eosinophils and mast cells.
He focuses on pathways involving a surface protein called Siglec-8 that is expressed on these cells as a possible target for future therapies.
Bochner, a professor of Allergy-Immunology in the Department of Medicine, joined Feinberg in July of 2013 after spending 28 years at Johns Hopkins University, where he began as a fellow training with Robert Schleimer, PhD, who is now chief of Allergy-Immunology at Feinberg.
What are your research interests?
I’ve always been interested in trying to find new treatments for my patients, especially when existing drugs are not adequate. As a result, my lab focuses on cells called eosinophils and mast cells. Eosinophils are one of the least common white blood cells. They help fight off parasite infections, but in certain diseases too many accumulate in specific tissues and cause trouble.
Mast cells, on the other hand, are normally found in virtually all tissues. But during allergic reactions, they get inappropriately activated to release their contents, including histamine and other substances. If enough mast cells get activated around the same time, a serious allergic reaction called anaphylaxis can occur.
Given the fact that mast cell activation can lead to serious life-threatening reactions, and that eosinophils are inappropriately increased and activated in a variety of conditions ranging from allergies, asthma, and sinusitis to certain skin diseases to gastrointestinal disorders such as eosinophilic esophagitis, the lab has been in search of ways to get rid of excess eosinophils and to prevent unwanted mast cell activation.
How does your research advance medical science and knowledge?
About 15 years ago, we discovered a surface protein uniquely shared by both eosinophils and mast cells called Siglec-8. When Siglec-8 is triggered, two important things happen: It causes eosinophils to die and disappear, and it makes it much harder to activate mast cells during an allergic reaction. We then discovered that Siglec-8 binds to unique sugar structures and that exposing these cells to sugar structures could kill eosinophils by binding to and activating Siglec-8.
As a result of our work and others, we now know that both Siglec-8 and its closest mouse counterpart, Siglec-F, bind sugars on certain types of mucus. We discovered that when the right type of mucus binds to Siglec-F on eosinophils, it causes them to die. And mice missing an enzyme necessary for putting these sugars onto the mucus accumulate more eosinophils in their airways in a model of asthma.
So we think that one way the body tries to protect itself from too many wayward eosinophils is by producing mucins on the mucosal surface that help get rid of these eosinophils. It’s our hope that Siglec-8 directed treatments might some day become available.
How is your research funded?
I am extremely grateful that this work has been funded for more than 15 years, mainly by the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute. I’ve also received funding from the Dana Foundation and worked with scientists at GlaxoSmithKline.
What types of partnerships are you engaged in across campus?
I have regular interactions with Ikuo Hirano, MD and Nimi Gonsalves, MD, ’02 ’05 GME, both in Medicine-Gastroenterology and Hepatology, because of their interest and expertise in eosinophilic gastrointestinal disorders. I also share patients that have eosinophilia with Brady Stein, MD, in Medicine-Hematology/Oncology.
Who makes up your research team?
Everyone here is new. First to join my lab at Feinberg was Daniela Janevska, a graduate student from the Driskill Graduate Program in the Life Sciences. Her PhD project focuses on understanding the mechanisms by which engaging Siglec-8 on an eosinophil initiates the intracellular signals that lead to cell death. Second was a postdoctoral fellow, Jeremy O’Sullivan, PhD. He has a strong background in cancer immunology and focuses on using Siglec-8 to target eosinophils and mast cells in various disease conditions, including cancers involving these cells. Third was Yun Cao, a senior research technologist whose main responsibility is to purify human eosinophils from blood of donors.
Next was research associate professor Liliana Moreno-Vinasco, PhD, an expert in mouse models of diseases including asthma. Since we are developing new strains of mice that express Siglec-8, her skills and expertise will be essential in establishing these important models and testing Siglec-8-based treatments.
Finally, two Medical Scientist Training Program graduates, now allergy fellows, have joined my lab. Jen Regan, MD, PhD, is working on a project involving prevention of anaphylaxis with a new drug. Melanie Dispenza, MD, PhD, will be working on another aspect of Siglec-8-based therapeutics. I never imagined this “dream team” coming together so quickly and effectively.