Established in 1972 by Charles Todd, City of Hope’s Department of Molecular Imaging & Therapy began at a time in which immune-based strategies for cancer were in their infancy. For example, there were no T-cell subsets and antibodies were all polyclonal. Todd, a chemist by training, was well known for his work on CEA (carcinoembryonic antigen), the best known tumor marker of its time, and his structural approach to immune problems. When monoclonal antibody technology became generally available in 1978, John Shively in Todd’s lab, produced a Mab to CEA that after genetic engineering and radiolabeling went into City of Hope patients as both an imaging and therapeutic agent.
Today, the Department of Molecular Imaging & Therapy continues to advance original vision, focusing simultaneously on immunology and on structural biology. The department has principal investigators (each of whom is aided by state-of-the-art facilities in mass spectrometry and NMR) and also features a computer cluster for the study of computational chemistry.
The unique combination of biological and structural studies at the Department of Molecular Imaging & Therapy, coupled with an intensive exploration of structure-function relationships, has created a thriving, productive environment and a fruitful collaboration among investigators at City of Hope and at other institutions.
Dr. Shively’s lab specializes in studying the CEA gene family. More specifically, he researches the use of anti-CEA antibodies for tumor imaging and therapy, as well as the role of CEACAM1 in T-cell activation and mammary epithelial cell polarization. Dr. Shively is also exploring the relationships of the immune system and genetics to fibromyalgia.
Edouard Cantin, Ph.D. — Studies Herpes simplex virus induced neuroinflammatory diseases
The Cantin lab focuses on understanding the pathogenesis of Herpes simplex virus 1 (HSV1) and other virus-induced neuroinflammatory diseases. The focus of Dr. Cantin's lab is on pathogenesis of encephalitis and ocular herpes stromal keratitis and the mechanisms that control reactivation of latent HSV infections. The lab is developing novel immunotherapeutic approaches to treat neuroinflammatory diseases, including studies involving manipulation of the microbiota and investigation of nutritional, pre- and probiotic interventions.
David Colcher, Ph.D.
— Developing new targeted imaging and therapeutic agents
Dr. Colcher’s group is focused on the development of targeted agents for the imaging and treatment of malignancies. His lab is working on both hematologic malignancies and solid tumors such as breast, prostate, gastric and colorectal cancer.
Markus Kalkum, Ph.D.
. - Employs mass spectrometry and proteomics to develop novel diagnostic assays and vaccines
Dr. Kalkum develops mass spectrometric methods for the quantitative analysis of proteins and other molecules in complex biological samples. He is generating novel biochemical assays for the ultrasensitive detection of functional biomolecules. His goal is to improve the early diagnosis and prevention of emerging and of frequently under-diagnosed diseases, including opportunistic fungal and bacterial He is advancing mycosis vaccine development and is studying immunomodulatory compounds of the gut microbiome. These activities are aimed to protect cancer patients from opportunistic infections, improving cancer treatment outcomes.
Nagarajan Vaidehi, Ph.D.
- Develops physics-based computational methods to study protein structure, dynamics and drug design
Dr. Vaidehi develops physics-based computational methods to study the structure, function, and dynamics of proteins and protein complexes. These methods are useful in studying protein-protein interactions and identify and optimize small molecule drugs to inhibit these interactions. Her specific interests are in studying the G-protein-coupled receptor dynamicas as in the interaction of chemokines, and antagonists to the chemokine receptors, that trigger leukocyte migration in immune response and inflammation. Prediction of the binding-site interactions of agonists and antagonists with the receptors greatly streamlines the drug development process.
The magnitude of an immune response is determined by the ratio of inflammatory vs regulatory T (treg) cells. Because the same pool of naïve T cells can differentiate into inflammatory effector T cells or inhibitory Tregs, generation of immune responses requires promoting the differentiation of inflammatory T cells while reciprocally inhibiting the formation of Tregs. Insufficient inflammatory T responses compromise immunity against pathogens, and overwhelming the Th17 responses can lead to autoimmunity such as multiple sclerosis, diabetes and systematic lupus erythematosus. Research in Dr. Sun’s laboratory is focused on understanding the mechanisms regulating T cell differentiation, and developing targeted therapeutics based on these mechanisms.