Birla Institute of Technology and Science, Pilani, India
All India Institute of Medical Sciences, New Delhi, India
University of Virginia, Charlottesville, USA
The focus of the lab centres on disorders of proliferation, including cancer and systemic autoimmune diseases, and the delineation of novel pathways and targets. Such studies are expected to extend theories of etiology.
Anjali Bose, Ruchi Sachdeva, Poonam Singh, Beneeta Kalha, Hritika Sharma, Ashok Kumar
Summary of Research
Humans are afflicted by several autoimmune diseases, the causes for many of which remain unknown. The pathological consequence of autoreactive immune responses are the subject of intense investigation. Systemic Lupus Erythematosus (SLE) is a prototypical non-organ specific autoimmune disease which generally manifests a life-long, relapsing-remitting phenotype. Multiple organs are targeted; chronic renal failure is a serious consequence, and patients can also exhibit arthritis, neurological involvement and hemolytic anemia. More than a hundred different autoantibody specificities have been described; drawing correlations between disease manifestations and autoimmune reactivity remains a high priority. Anti-phospholipid autoreactivity, a frequent occurrence in systemic autoimmune disease, has been associated with autoimmune hemolytic anemia, thrombotic events and early pregnancy loss. The immunological and physiological sequelae arising as a result of the release of sequestered hemoglobin in animals prone to autoimmunity form a focus of current investigations. Interestingly, in both SLE patients and in animals prone to systemic autoimmunity, aberrance in apoptotic processes has been observed. Excessive spontaneous apoptosis (or excessive susceptibility to apoptotic stimuli) as well as inefficient clearance of apoptotic debris have been documented in lupus patients, and animals genetically modified to impair the uptake of apoptotic cells exhibit lupus-like pathology. Autoimmune cascades initiated by early autoantibody responses specifically directed towards apoptotic cells are being investigated; since apoptotic debris appears to constitute the original antigenic insult, it is conceivable that such events could have a bearing on pathology. Human chorionic gonadotropin (hCG), a placental glycoprotein hormone, stimulates the release of progesterone from the corpus luteum, thereby sustaining pregnancy; successful pregnancy is believed to represent a Th2 skew. Given reports of pregnancy-associated lupus flares in humans and the ameliorating influence of hCG in murine models of organ-specific (Th1-mediated) autoimmune disease, the effects of administration of the hormone in animals genetically prone to systemic autoimmunity (a state which, like pregnancy, can also be notionally considered to constitute a Th2 skew, given associated hypergammaglobulinemia and antibody-mediated pathology) are being investigated. In recent years, hCG has been shown to be secreted by a variety of cancers as well, and its presence has been associated with chemo-resistance as well as with poor patient prognosis. Understanding the molecular pathways by which hCG potentially impacts on tumor progression, as well as the development of novel immunotherapeutic anti-hCG vaccination strategies, form another focus of the laboratory.
- A vaccine that prevents pregnancy in women. Talwar GP, Singh O, Pal R, Chatterjee N, Sahai P, Dhall K, Kaur J, Das SK, Suri SK, Buckshee K, Saraya L, Saxena BN (1994). Proceedings of the National Academy of Sciences (USA) 91: 8532-8436.
- Absence of corpus luteum rescue by chorionic gonadotropin in women immunized with a contraceptive vaccine. Pal R, Singh O (2001) Fertility and Sterility 76: 332-336.
- Evidence for multiple shared antigenic determinants within Ro60 and other lupus- related ribonucleoprotein autoantigens in human autoimmune responses. Pal R, Deshmukh U, Ohyama Y, Fang Q, Kannapell CC, Gaskin F, Fu SM (2005) The Journal of Immunology 175: 7669-7677.
- Anti-idiotype mediated epitope spreading and diminished phagocytosis by a human monoclonal antibody recognizing late-stage apoptotic cells. Gandhi R, Hussain E, Das J, Handa R, Pal R (2006) Cell Death and Differentiation 13: 1715-1726.
- Endogenous humoral autoreactive immune responses to apoptotic cells: Effects on phagocytic uptake, chemotactic migration and antigenic spread. Das J, Arora P, Gracias D, Praveen A, Raj BPJ, Martin E, Pal R (2008) European Journal of Immunology 38: 3561-3574.
- Serum and organ-associated anti-hemoglobin humoral autoreactivity: Association with anti-Sm responses and inflammation. Bhatnagar H, Kala S, Sharma L, Jain S, Kim KS, Pal R (2011) European Journal of Immunology 41: 537-548.
- Transgenesis-mediated reproductive dysfunction and tumorigenesis: Effects of immunological neutralization. Sachdeva R, Bhardwaj N, Huhtaniemi I, Aggrawal U, Jain SK, Zaidi R, Singh O, Pal R (2012) PLoS ONE 7: e51125.
- Synergistic activation of innate and adaptive immune mechanisms in the treatment of gonadotropin-sensitive tumors. Bose A, Huhtaniemi I, Singh O, Pal R (2013) PLoS ONE 8 e61288.
- Gonadotropin-mediated chemoresistance: Delineation of molecular pathways and targets. Sahoo S, Singh P, Kalha B, Singh O, Pal R (2015) BMC Cancer 15: 931. doi: 10.1186/s12885-015-1938-x.
- Elucidation of the potential disease-promoting influence of IgM apoptotic cell-reactive antibodies in lupus. Malik M, Arora P, Sachdeva R, Sharma L, Ramachandran VG, Pal R (2016) Lupus doi: 10.1177/0961203315624023.
- Innate and humoral recognition of the products of cell death: Differential antigenecity and immunogenecity in lupus. Arora P, Malik M, Sachdeva R, Saxena L, Das J, Ramachandran VG, Pal R (2016). Clinical and Experimental Immunology doi: 10.1111/cei.12889.
- Gonadotropin and tumorigenesis: Direct and indirect effects on inflammatory and immunosuppressive mediators and invasion. Khare P, Bose A, Singh P, Singh S, Javed S, Jain SK, Singh O, Pal R. (2017) Molecular Carcinogenesis 56: 359-370.
- Relevance of Wnt10b and activation of β-catenin/GCMa/syncytin-1 pathway in BeWo cell fusion. Malhotra S, Baanerjee P, Chaudhary P, Pal R, Gupta SK (2017). American Journal of Reproductive Immunology doi:10.1111/aji.12676.