Research

Bone Neoplasia refers to abnormal bone growth, and this can sometimes include tumors located in the bone tissue. This program’s primary goal is to understand the formation of primary and secondary tumors that develop in the bones.

Bone is a storage source of cytokines (proteins used for cell signaling) which are critical to tumor production. Because of this, bone is an important site of metastasis for breast and prostate as well as other types of cancer. The development of a primary bone tumor appears to be caused by the deregulation of the normal bone development process. A better understanding of the normal processes that take place during bone remodeling, when old bone tissue is reabsorbed, and new bone tissue is created, will improve our understanding of these same processes that are unregulated during both primary and secondary tumor development.

Chaired by Marc Hansen, Ph.D., this group is comprised of faculty from multiple disciplines and interacts with the Musculoskeletal Signature Program.

This program was created in 2013 under the leadership of Dr. Cheryl Oncken. It consists primarily of smoking cessation/reduction and pregnancy, a Colon Cancer Prevention Program, Cancer epidemiology (particularly breast and colorectal cancers), a breast imaging study, and a lung cancer screening program.

The smoking cessation area, led by Dr. Cheryl Oncken, is an academically solid, NIH-funded program of long standing, but is not necessarily tied to cancer.

The Colon Cancer prevention area is a multi-disciplinary translational effort founded by Drs. Daniel Rosenberg and Joel Levine >10 years ago. This NIH-funded program is unique regionally, and is among the very few such research-clinical integrated programs nationally. Its program objectives are:

1. To create large cohorts of patients at risk for colon cancer integrating basic and applied science into long term clinical risk reduction
2. To establish, by longitudinal follow up of patients, data sets for the analysis of risk factors and interventions to prevent colon cancer
3. To encourage CCPP patients to participate in investigator initiated basic science projects
4. To develop new approaches to population based colon cancer risk assessment and reduction

Its program status by objective can be summarized thus:

• Mechanisms that govern the formation of precancerous colon lesions (aberrant crypt foci) and their conversion to advanced neoplasia – using genetic, and biochemical tools adapted to the analyses of specimens of extremely limiting size.
• CCPP has approximately 1,500 patient visits annually including 500-600 new patients. The New patient/Endoscopy ratio is essentially 1:1 (ratio goal for private practice) and all are referred to the GI Division for procedures.
• CCPP has developed patient cohorts including: Vitamin D and Colon Cancer Risk (2,000 patients); FIT and Interval Screening (1,500); Risk profiles by NCI Risk Assessment Tool (5,000 +)
• CCPP has enrolled over 400 patients in a funded study of the Molecular Biology of Aberrant Crypt Foci and the largest ACF Tissue Repository (Rosenberg Lab)
• CCPP has created, in partnership with the School of Pharmacy, a funded pilot (CHIP) based on Community Pharmacist Certification in Colon Cancer Risk and Prevention coupled with FIT based screening in underserved populations.

Its projects in development include:

• Data gathering and analysis for follow up of Vitamin D/Adenoma Risk - 1,600 patients including data on Vitamin D replete patients and subsequent surveillance at 3 and 5 years.
• Study of FIT + polyps for increase in microvasculature (Polyp Staining or Pixel Map of NBI images)
• Grant submission for Micro biome patterns in Colon Cancer Risk (Convergence - Storrs)
• Risk Model for Colon Cancer using FIT status integrated into standard demographic risk profile (AKE - LEX Artificial Intelligence and Adaptive Knowledge Engine)
• Develop Methodology for UConn Health wide “Colon Cancer Risk and Prevention Value Proposition.” This will include review and education of “best practice,” data analysis for status and improvement in Cost/Quality and ongoing access for health care providers to advances in Prevention strategies

Our Team

Cheryl Oncken, M.D., M.P.H.
Daniel Rosenburg, Ph.D.
Joel Levine, M.D.
Alicia Dugan, Ph.D.
Helen Swede, Ph.D.
Ethan Bortniker, M.D.

This is one of the longest running basic/translational cancer programs at UConn Health. It was initiated less than 30 years ago by Dr. Bijay Mukherji, who was the first to publish generation of a CD8+ cytotoxic T lymphocyte clone against a human tumor (melanoma) in 1983. The Mukherji lab has been continuously funded by NCI for several decades.
Other aspects of the program include:

• T cell response, including regulation, to human melanoma (Mukherji Lab)
• Harnessing co-stimulation for immunotherapy (Vella Lab)
• T cell tolerance (Adler Lab)
• Sentinel node B cells as novel sources of anti-tumor antibodies (Claffey Lab)
• TILs as prognosticators of overall survival in bladder cancer (Clement Lab)
• Mouse models of mutated BRAF-driven melanomas (Khanna Lab)

Two aspects of the Cancer Immunology and Immunotherapy (CII) program, funded substantially by the NCI, have garnered wide attention. One is the identification of heat shock proteins (of hsp70 and hsp90 families) as chaperones of antigenic peptides. This work from the Srivastava lab has been published in the top tier journals over about 25 years, and lead to the first ever personalized human cancer immunotherapy; Oncophage or Vitespen for renal cancer, which is made for each patient from their heat shock protein-chaperoned peptidome, was approved for clinical use in Russia in 2008. The Alliance co-operative group (supported by CTEP/FDA) is now conducting randomized trials of Oncophage in recurrent glioblastoma multiformae (ongoing at 50 U.S. centers).

The second notable aspect is the genomics-driven antigen identification for immunotherapy. This approach was first suggested by the Srivastava Lab in 1993. This is very active area of basic and translational research at the Neag Comprehensive Cancer Center and has the following major components:

• First genomics-driven immunotherapy clinical trial to start at the Neag Comprehensive Cancer Center 2016, March.
• Defining the rules of what makes a good anti-cancer immunogen, using complete exome and transcriptome sequencing of human cancers and linked normal tissues.
• Genomic analysis of responding and non-responding melanoma lesions to checkpoint blockade (collaboration with MSKCC) – ongoing.
• Prospective stratification of bladder cancers and melanomas by mutational burden before checkpoint blockade (collaboration with MSKCC – ongoing).

Our Team

Pramod Srivastava, Ph.D., M.D.
Upendra Hegde, M.D.
Tony Vella, Ph.D.
Kevin Claffey, Ph.D.
Henry Smilowicz, Ph.D.
Adam Adler, Ph.D.

A variety of studies in cancer cell biology are assembled in this program. Although each component is academically solid, the program has not yet melded into a coherent theme, and is a work-in-progress.

Its components include:

• Iron transport and cancer
• Cyclin biology and biochemistry
• Genetics of endocrine tumors
• Genetic changes from pre-cancerous lesions to malignant colon cancers
• Mismatch repair in cancers
• Signaling pathways controlling proliferation and organization of cytoskeleton
• Protein-protein interactions on a global scale

Our Team

Suzy Torti, Ph.D.
Kevin Claffey, Ph.D.
Chris Heinen, Ph.D.
Andrew Arnold, M.D.
Doug Peterson, D.M.D., Ph.D.
Bruce Mayer, Ph.D.

Led by Andrew Arnold, M.D., there are many faculty members engaged in laboratory research in the Center for Molecular Oncology.

Dr. Arnold's laboratory investigates the basis of tumors of the endocrine glands on a molecular and genetic level. The cyclin D1 oncogene, initially discovered by Dr. Arnold in parathyroid tumors, has a broad role in human cancer, and its action in breast cancer is specifically being investigated. Dr. Arnold's laboratory is also pursuing their recent discovery of the major genetic basis of parathyroid gland cancers.

Our Team

Andrew Arnold, M.D.
Jessica Costa, D.M.D., Ph.D.
Anne Delany, Ph.D.
Marc Hansen, Ph.D.
Christopher D. Heinen, Ph.D.
Masako Nakanishi, Ph.D.
Daniel Rosenberg, Ph.D.

In addition to caring for individuals with sickle cell disease, the New England Sickle Cell Institute conducts research aimed at developing new treatments for the disease.

Led by Biree Andemariam, M.D., the New England Sickle Cell Institute is dedicated to providing quality patient care to adults living with sickle cell disease.

For more information on research and clinical trials opportunities, please visit the Clinical Research website.

The Center for Vascular Biology conducts state-of-the-art research in the area of tumor angiogenesis (the formation of new blood vessels from pre-existing ones to feed a tumor) and lipid mediators (chemical messengers that can stimulate an immune response). There is also research focused on signal transduction, vascular proteins, post-transcriptional gene expression, vascular developmental biology and cell invasion/metastasis.