Current QIMR Berghofer appointment
- 1998-current: Laboratory Head, QIMR Berghofer.
- 2010-2015: NHMRC Senior Principal Research Fellow, QIMR Berghofer.
- 2005-2009: NHMRC Principal Research Fellow, QIMR.
- 2001-2004: Sylvia & Charles Viertel Foundation Senior Research Fellow, QIMR.
- 2001: NHMRC Senior Research Fellow – declined.
- 1998: Research Fellow, QIMR.
- 1996: Senior Research Officer, QIMR.
- 1991-1995: Research Officer, QIMR.
- 1989-1990: Research Officer, University of Adelaide.
Current Area of Research
Our goal is to understand DNA damage surveillance pathways that maintain genome stability in response to endogenous and exogenous sources of DNA damage in the normal and disease state. This is an area of critical importance to cancer research as the pathway controlling the DNA damage response (DDR) are involved in tumor suppression and are believed to be mutated at an early stage in the evolution of cancer. Several genes involved in the DNA damage response pathways when functionally compromised (ATM, BRCA1, BRCA2 and PALB2) can contribute to breast cancer formation.
Paradoxically, many conventional cancer treatments elicit the generation of additional DNA damage to exploit inherent DDR faults present in tumour cells. Tumours can survive these DNA damaging insults by relying on or activating compensatory DNA repair pathways to repair the lesions, leading to cancer recurrence. The underlying theme of our research program is to exploit this dysregulation of the DDR and oncogenic signaling pathways in breast cancer to develop new targeted therapeutic approaches. Our research is multidisciplinary encompassing cell and molecular biology, proteomics, systems biology, mouse genetics (knockout and overexpression models), and preclinical studies using tumor cell lines and patient-derived tumor xenografts. Our work is likely to have implications for the development of future cancer therapies with relevance to both killing of cancer cells and protection of normal cells.
My group has made numerous contributions in understanding the normal functions of the ATM protein, a central controller of cellular responses to DNA damage and how it suppresses cancer. These include characterization of several interacting partners and substrates for ATM kinase (c-Abl, p53, Nibrin, BRCA1, CHK1 and CHK2). We also identified and functionally characterized the Cep55 protein as a new regulator of cytokinesis, the final stage of cell division that divides the cytoplasm equally amongst two daughter cells. More recently, we identified two novel Single-Stranded DNA (ssDNA) Binding proteins, named as SSB1 and SSB2, which play a critical role in the maintenance of genomic stability. Through our NHMRC funded Program grant we have worked actively to bridge the gap between basic and applied research. My group has developed a novel combination therapy against breast cancer, involving targeted radioimmunotherapy with a DNA repair inhibitor and chemotherapy. We have also performed functional screens and have discovered therapeutic targets that regulate primary tumor growth and metastasis of triple-negative breast cancer.
Some of the relevant publications are highlighted below:
- Identified C-Abl as first partner protein of ATM kinase (Nature 1997, 386, 520-23).
- Provided evidence for physical interaction between ATM and p53 tumor suppressor (Nature Genetics 1998, 20: 398-400).
- Provided biochemical explanation for the overlap of cellular phenotypes of the two genetic diseases Ataxia-Telangiectasia and Nijmegen-Breakage Syndrome (Nature Genetics 2000, 25: 115-19).
- Provided evidence for direct regulation of breast cancer susceptibility gene product (BRCA1) by ATM kinase (Cancer Research (2000): 60:3299-304).
- Demonstrated for the first time that certain mutations in ATM are associated with high penetrance for breast cancer in multiple-case breast cancer families (J Natl Cancer Inst . 2002, 94: 205-215).
- Provided evidence for the direct role of protein phosphatase 2A in the regulation of ATM activation and activity. (EMBO J 2004, 23:4451-4461).
- Functionally characterized a novel protein, named as Cep55, involved in regulation of cytokinesis (Development Cell, 2005, 9: 477-488).
- Identified and functionally characterized two novel single stranded DNA binding proteins which play crucial role in maintenance of genome stability (Nature 2008, 453:677-81).
- Developed a combined modality therapy for Triple-negative breast cancer using radioimmunotherapy combined with DNA repair inhibition for effective cancer treatment. (J Nuc Med 2013, 54(6):913-21).
- Demonstrated previously unreported importance of DNA repair gene, Rad51, in progression and metastasis of sporadic breast cancer (Oncotarget 2014 5(10):3261-72).
- Demonstrated CDK-dependent regulation of EXO1 at sites of DSBs, to enable cells tochoose a particular DNA repair pathway (Nature Commun 2014, 5:3561).
- Australian Society of Medical Research.
- Australian Society for Biochemistry and Molecular Biology.
- National Association of Research Fellows.
- American Association of Cancer research.
- Asia-Pacific International Molecular Biology Network.
- 2001: Ralph-Doherty QIMR Berghofer Excellence in Science Prize.
- 1998: PE Biosystems QIMR Berghofer Research Achievement Award.
- 1996: Leukaemia Foundation of Queensland Travel Award.
- 1994: American Association of Cancer Research Young Investigator Travel Award.
- 1985-1988: Open Research Fellowship from Indian Council of Medical Research (ICMR), New Delhi (India).
- 1983: Certificate of Merit for academic performance during Postgraduate studies.
- 1981-83: Merit Scholarship from Panjab Uni, India in MSc. Honours in microbiology.
- 1978-81: Merit Scholarship from Panjab Uni, India in BSc. Honours in microbiology.
Professor Khanna has successfully attracted peer-reviewed funding from national and international agencies. These include NHMRC-funded Program and Project Grants, Australian Research Council, National Institutes of Health (USA), US Department of Defense Novel Concept Award, Susan G Komen Breast Cancer Foundation USA, Queensland Cancer Fund/Cancer Council Queensland, National Breast Cancer Foundation Infrastructure and Novel Concept grants and Australian Cancer Research Foundation Infrastructure grant.
Professor Khanna has served as a panel member and chair on many national and international granting agencies including Human Science Frontiers Fellowship, National Breast Cancer Foundation Practitioner and Early Career Fellowships, NHMRC Early Career Fellowship, NHMRC Assigners Academy and Grant Review Panel, Victorian Cancer Agency Seed and Translational Grant Panel.
- 1993: MSc Microbiology, Panjab University.
- 1989: PhD Parasitology, Postgraduate Institute of Medical Education and Research.
- 1981: BSc Hons Microbiology, Panjab University (India).