Dr Rajnikant Patel

I studied Pharmacy at the University of London (1980) and did my PhD in biochemical pharmacology at the University of Aston in Birmingham (1985). My thesis involved the development of an in vitro model to study the effect of anti-inflammatory drugs on leucocyte migration. I did my post-doctoral work with Michael Whittaker at University College London where I examined the regulation of cell division in sea urchin embryos. The award of a Wellcome Trust Fellowship (1993) allowed me to move to Leicester and continue my research in David Critchley’s laboratory in the Department of Biochemistry (now Molecular and Cell Biology). I was appointed to a lectureship in 2000.

How a mammalian cell segregates its chromosomes into two identical sets at mitosis is still unclear. Mistakes in this process result in the generation of aneuploid cells which then have the potential to form cancer cells. The cohesin ring-complex holds the sister chromatids together following DNA replication. Cohesin comprises Smc1 and Smc3 (members of the structural maintenance of chromosomes family of ATPases) scc1 (a member of the kleisin family of proteins) and scc3 (SA1 and SA2 in vertebrates). However less is known about the cohesin regulators such as Wings Apart-like 1 (Wap1) and Pds5 (Precocious Dissociation of Sisters) and how they control the loading and removal of cohesin from chromatin.

We also study the mitotic checkpoint (or spindle assembly checkpoint/SAC) and its regulation of cell survival/cell death. Many anti-microtubule anti-cancer drugs such as Taxol (Paclitaxel) activate the SAC and arrest the cell in mitosis which then undergo programmed cell death or apoptosis although the mechanism remains unclear. Our current studies aim to understand the biochemical events that determine the fate of the cell in response to SAC activation.

Darweesh, O., Al-Shehri, E., Falquez, H., Lauterwasser, J., Edlich, F., & Patel, R. (2021). Identification of a novel Bax-Cdk1 signalling complex that links activation of the mitotic checkpoint to apoptosis. J. Cell Sci., 134(8), doi:10.1242/jcs.244152.

Al-Jomah, N., Mukololo, L., Anjum, A., Al Madadha, M., & Patel, R. (2020). Pds5A and Pds5B Display Non-redundant Functions in Mitosis and Their Loss Triggers Chk1 Activation. Front. Cell Dev. Biol., 8, doi:10.3389/fcell.2020.00531.

Hagemann, C., Weigelin, B., Schommer, S., Schulze, M., Al-Jomah, N., Anacker, J., Gerngras, S., Kuhnel, S., Kessler, A. F., Polat, B., Ernestus, R-I., Patel, R. and Hamilton-Vince, G. (2010). The cohesin-interacting protein, precocious dissociation of sisters 5A/sister chromatid cohesion protein 112, is up-regulated in human astrocytic tumors. Int. J. Mol. Med. 27, 39-51.

Hagemann, C., Stojic, J., Gerngras, S., Kuhnel, S., Said, S. M., Patel, R., Kammerer, U., Vordermark, D., Roosen, K. and Hamilton-Vince, G. (2008). Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (Microcephalin) and MCPH5 (ASPM, abnormal spindle- like microcephaly associated) in human malignant gliomas. Oncology Reports, 20, 301-308.

Mistry, P., Deacon, K., Mistry, S., Blank, J. & Patel, R. (2004). NF-kappa B promotes survival during mitotic cell cycle arrest. J Biol. Chem. 279, 1482-1490.  

Patel, R., Holt, M., Philipova, R., Moss, S., Hidaka, H., Schulman, H. & Whitaker, M. (1999).  Calcium/calmodulin-dependent phosphorylation and activation of human cdc25-C at the G2/M-phase transition in HeLa cells. J.Biol.Chem. 274, 7958-7968.

Torok, K., Wilding, M., Groigno, L., Patel, R. and Whitaker, M. (1998). Imaging the spatial dynamics of calmodulin activation during mitosis.  Curr. Biol. 8, 692-699.

Wilding, M., Wright, E. M., Patel, R., Ellis-Davis, G. and Whitaker, M. (1996). Local perinuclear calcium signals associated with mitosis-entry in early sea urchin embryos. J. Cell Biol., 135, 191-199.

Edgecombe, M., Patel, R. & Whitaker, M.J. (1991). A cyclin-abundance cycle-independent p34cdc2 tyrosine phosphorylation cycle in early sea urchin embryos. EMBO J., 10, 3769-3775.

Whitaker, M.J. & Patel, R. Calcium and cell cycle control. (1990). Development 108, 525-542

Twigg, J., Patel, R. & Whitaker, M.J. (1988). Translational control of InsP3 induced chromatin condensation during the early cell cycles of sea urchin embryos. Nature 332, 366 369.

Currently there are 3 PhD students in the lab. We also host MSc and undergraduate project students. Our research focuses on two aspects of the cell cycle. First to understand how sister chromatid cohesion is regulated during the cell cycle (doi:10.3389/fcell.2020.00531). Future projects in this area will examine the mechanism of cohesin loading and unloading by regulatory proteins such as Pds5 Wapl and Esco1/2. Second to understand how mitotic cell cycle arrest induced by specific anti-cancer drugs such as Taxol leads to apoptotic cell death (doi:10.1242/jcs.244152). Further work in this area will examine the how Cdk1 interacts with other components of the apoptotic pathway such as Bak Bcl-2 Bcl-xl and Mcl-1.

Work in our lab uses biochemical assays molecular and cell biology techniques to alter gene function and high-resolution microscopic analyses of both fixed and living cells to address these questions. 

I teach on the following courses:

MSc Cancer Cell and Molecular Biology (course convenor)

BS2092 (Molecular and Cell Biology)

BS3003 (Cancer Cell and Molecular Biology)(module co-convenor)

Cell division and cancer

Anti-cancer drugs

Member of the Biochemical Society

Member of the British Society of Cell Biology

Member of the Royal Pharmaceutical Society of Great Britain