Laboratory of Animesh Barua, PhD

The main focuses of the lab are (1) to establish an early detection test for ovarian cancer (OVCA) using molecular-targeted ultrasound imaging in association with serum markers, and (2) to explore the prevention of OVCA incidence and its recurrence by enhancing anti-tumor immune function through dietary supplements. In addition, our lab is also exploring the factors associated with the malignant transformation of uterine fibroids (leiomyoma, a benign tumor) to leiomyosarcoma, a lethal cancer of the uterus. Moreover, our lab is also involved in examining the tumor-induced immunosuppression in cervical cancer and its prevention.

Ovarian cancer is an aggressive and fatal malignancy of women with a heterogeneous source of origin including ovarian surface epithelium (OSE) or fimbrial surface epithelium (FSE). OVCA in most cases is detected at late stages with frequent recurrence and high case to death ratio among gynecological malignancies. In contrast, the 5-year survival rates of OVCA patients increases to more than 90% when it is detected at early stages. However, early detection of OVCA is happenstance as the symptoms are non-specific at early stage and no test for effective early detection of OVCA is available. Serum levels of CA-125 alone or in combination with traditional ultrasound imaging are the currently used tests for OVCA detection. Serum levels of CA-125 are not specific for early OVCA. In addition, the resolution of traditional ultrasound imaging is limited and cannot detect early changes associated with ovarian malignancy. Moreover, no target(s) in the ovary indicative of malignant transformation to be detected by ultrasound imaging has been established. Thus, an effective early detection test for OVCA is urgently needed. Our early detection of OVCA project determines the expression of tumor-associated protein markers by the ovary and determines if these proteins are shed into the serum. Our laboratory develops imaging agents to test the feasibility of these markers as targets to be imaged by molecular-targeted ultrasound imaging. Subsequently, prevalence of these marker(s) in serum are determined. Using a preclinical model of spontaneous OVCA (laying hens), the ability of these serum and imaging markers are being tested for early detection of OVCA.

Tumor-induced immunosuppression is one of the hallmarks of tumor progression. Natural Killer (NK) cells are the first line of defense against a developing tumor. The mode of dissemination of OVCA differs from other cancers in that it spreads through diffusion in the peritoneal cavity. Thus, local immune function plays a critical role in preventing OVCA metastasis. However, the tumor evolves mechanisms to avoid NK-cell mediated anti-tumor immunity. Our laboratory is examining the efficacy of natural product supplementation in enhancing anti-tumor immune functions of NK cells.

Uterine fibroids are benign tumors of women of reproductive age commonly associated with heavy bleeding and extreme pain. Moreover, a subset of these benign tumors develops to lethal malignant leiomyosarcoma. Our laboratory examines the factors associated with transformation of uterine fibroids to leiomyosarcoma and prevention of fibroid incidence using a spontaneous preclinical model.

Our work

Current projects in our laboratory:

1. Ovarian cancer: a) Factors associated with malignant transformation of the ovary and fimbria of fallopian tube; b) Early detection of ovarian cancer by serum markers and molecular-targeted ultrasound imaging; c) Prevention of ovarian tumor-induced immunosuppression by dietary supplementation of Ashwagandha.
2. Uterine leiomyosarcoma: Uterine fibroids are benign tumors of women of reproductive age. A subset of these tumors become uterine leiomyosarcoma, a highly lethal malignant tumor of the uterus. This project explores the causative pathways leading to this malignant transformation.
3. Cervical cancer: Progression of cervical cancer is facilitated by immunosuppression in the tumor microenvironment. This project explores tumor-induced expression of immunosuppressive receptors and their effects on tumor induced immunosuppression.
4. Endometriosis: Endometriosis is a pathological condition of female reproductive organs which affects reproductive functions, a risk factor for development of cancer and required pain medication. This project explores the expression of receptors for non-opioid medication to control pain associated with endometriosis. 

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Technology and methods

Our laboratory hosts the Rush Proteomics and miRNA Core facilities. Our laboratory has expertise on the following techniques and methodology:  

• Detection of serum and tumor biomarkers using various Proteomics Technology.
• Gene expression and microRNA analysis using qRTPCR and other advanced Genomic techniques.
• Development of molecular-targeted ultrasound imaging agents for detection of tumors.
• Extraction of protein and total RNA from formalin fixed paraffin embedded tissues.
• Immunohistochemical and cell culture techniques.
• An animal model of spontaneous ovarian cancer and uterine fibroids.
• Use of natural products as supplementation to enhance anti-tumor immune function.

Figures showing examples of technologies used in current projects:

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Publications

• Barua et al., Anti-tumor and anti-ovarian autoantibodies in women with ovarian cancer. Am J Reprod Immunol. 2007; 57(4):243-9. PMID: 17362385
• Barua et al., Detection of ovarian tumors in chicken by sonography: a step toward early diagnosis in humans? J Ultrasound Med. 2007; 26(7):909-19. PMID: 17592054
• Barua et al., Histopathology of ovarian tumors in laying hens: a preclinical model of human ovarian cancer. Int J Gynecol Cancer. 2009; 19(4):531-9. PMID: 19509547
• Khan et al., Expression of Leukocyte Inhibitory Immunoglobulin-like Transcript 3 Receptors by Ovarian Tumors in Laying Hen Model of Spontaneous Ovarian Cancer. Transl Oncol. 2012 5(2):85-91. PMID: 22496924
• Barua et al., Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer. Am J Reprod Immunol. 2013; 70(6):538-50. PMID: 24188693
• Barua et al., VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer. Ultrason Imaging. 2015; 37(3):224-37. PMID: 25294846

A full list of Animesh Barua, PhD’s research publications can be found on PubMed.

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Funding

Current funding:

• NIH R21CA187309: Ashwagandha supplementation enhances ovarian tumoricidal activity of NK cells.
• NIH R01CA210370: Early detection of ovarian cancer by targeted ultrasound imaging and serum marker.
• Swim Across America: Early detection of ovarian cancer by serum markers.
• The Portes Foundation: Serum markers of ovarian cancer- associated malignant changes in the oviductal fimbria.

Past grants (Selected):

• W81XWH-10-1-0523: Idea Development Award: Early Detection of Ovarian Cancer by Contrast- Enhanced Ultrasound-Targeted Imaging.
• W81XWH-11-1-0510: Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis.
• W81XWH-12-1-0460: Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound.
• W81XWH-14-1-0315: Tumor-Associated Microvessel Targeted Ultrasound Molecular Imaging Probes Detect Ovarian Cancer at Early Stage.
• NCI/Pacific Ovarian Cancer Research Consortium (POCRC) (2009-11): Career development grant.

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Our team

Team consists of collaborators from diverse fields of expertise including pathology (Pincas Bitterman, MD), ultrasound imaging (Jacques Abramowicz, MD), gynecologic oncology (Sameer Sharma, MD), Avian reproduction (Janice Bahr, PhD), Biostatistics (Sanjib Basu, PhD) and Bioinformatics.

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Awards and honors

A. Barua, PhD

• 2005: Travel grant for best Abstract, Annual meeting of the Society for the Study of Reproduction (SSR). Quebec city, Quebec, Canada.
• 2006: Rush Chapter of Sigma Xi best poster presenter in fellow/instructor category. 23rd Annual Rush University Forum for Research and Clinical Investigation, Chicago, IL.
• 2006: Scholar-in-Training Award, American Association for Cancer Research (AACR). First AACR International onference on Molecular Diagnostics in Cancer Therapeutic Development, Chicago, IL.
• 2007: Scholar-in-Training Award, American Association for Cancer Research (AACR). Sixth AACR International Conference on Frontiers in Cancer Prevention Research, Philadelphia, PA.
• 2012: Mentor of the Year, Graduate College, Rush University: Voted by graduating students.
• 2013: Mentor of the Year, Graduate College, Rush University: Voted by graduating students.
• 2014: Graduation Hooder for MS students, Graduate College, Rush University: Voted by graduating students.
• 2015: Graduation Hooder for MS students, Graduate College, Rush University: Voted by graduating students.
• 2016: Exceptional teacher of the year: 2016, Graduate College, Rush University: Voted by the graduating students.
• 2017: Graduation Hooder for MS in Biotechnology students, Graduate College, Rush University: Voted by graduating students.
• 2017: Co-Chair of the 37th Annual meeting of the American Society for Reproductive Immunology, September 17-20, 2017, Chicago, IL.    

A. Yellapa, PhD, Postdoctoral fellow/Instructor, Department of Cell & Molecular Medicine

• 2014: Paul E. Carson, MD Award for excellence in Pharmacology for doctoral student.
• 2017: Rush Chapter of Sigma Xi best poster presenter in fellow/instructor category. 34th Annual Rush University Forum for Research and Clinical Investigation, Chicago, IL.

Shenon Sethi, MD, Resident physician (Pathology), Rush University Medical Center

• 2017: Rush Chapter of Sigma Xi, 3rd best poster presenter in fellow/instructor category. 34th Annual Rush University Forum for Research and Clinical Investigation, Chicago, IL.

K. A. Kadela, MD, Former student

• 2013: Winner of the Rush Medical College Award at the Rush Research Forum. Rush Medical College.

Rachel Kapadia, MS in Pharmacology (Graduate of 2014)

• 2014: Rush Chapter of Sigma Xi best poster presenter in fellow/instructor category. 31st Annual Rush University Forum for Research and Clinical Investigation, Chicago, IL.

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Contact

Animesh Barua, PhD
Associate Professor,
Laboratory for Translational Research on Ovarian Cancer,
Departments of Anatomy & Cell Biology, Pathology and OB/GYN

Director, Rush Proteomics and miRNA Core facility,
Room # 410, Cohn Building,
Rush University Medical Center,
1735 W. Harrison St.,
Chicago, IL 60612
Tel: 312-942-6666
Fax: 312-563-3552
Email: animesh_barua@rush.edu

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