We are keen on hearing from driven and conscientious PhD candidates. We provide mentorship to UG and PGR students interested in the following research areas. Research projects:
1. Regenerative medicine and stem cells, paradigm: human urinary tract, bone and bone marrow
Question: Can we identify aberrations of normal development/ageing towards therapeutic exploitation?
I was the first scientist to develop and establish induced pluripotent stem-cell (iPSC) technology at the Northern Institute for Cancer Research, Newcastle University. My PhD study was the first to establish a novel iPSC-derived urinary tract model in regenerative medicine (Pal,D., Moad, M. et al ,European Urology 2013, Impact factor = 17, 59 citations; Pal,D et al, European Urology, 2013).
Our aim is to define key processes in human development through differentiation of stem cells as well as de-differentiation of terminal cells to their primitive precursors. This will not only form the basis of tissue engineering but will also reveal key insights into ageing as well as potentially identify targetable aberrations of “normal” development leading to diseases such as cancer.
2. 3Rs compliant non animal technologies[organoids], paradigm: human bone marrow
Question: Can we engineer faster, better and cheaper synthetic patient-microtissues ex vivo through automation?
Cancer drug development is hindered by high drug attrition rates. Preclinical testing in leukemia is severely obstructed by lack of models that can test efficacy on patient-cancer cells within rapid turnaround times. Despite its aggressiveness primary leukemia cells rapidly die in tissue culture due to which there is a heavy dependence on cell line models. Cell lines being adapted to niche-independent suspension cultures do not represent the molecular complexity at disease diagnosis. Some primary patient cells can be studied in animal models, but these are expensive, ethically debatable and do not deliver drug response data within clinically relevant time-frames. I addressed these issues by developing an artificial human bone marrow which enabled successful culture and hence drug testing on patient-derived cancer cells (Pal,D. et al, Leukemia, 2016, Impact factor = 11, 18 citations, F1000 prime recommended; Martinez-Soria-N.et al, Cancer Cell, 2019, impact factor = 22, citations = 12). I was the first scientist to establish this approach in Wolfson Childhood Cancer Research Centre, Newcastle University which for the very first time allowed us to culture, proliferate and work directly with patient-cancer blasts. Having secured a national NC3Rs fellowship I further advanced my work through induced pluripotent stem cell engineering to re-create the different cellular constituents of the human bone marrow on a petri-dish. This means we can now define niche dependence within the dynamic plasticity of the bone marrow.
Developing a multicellular bone marrow is technically challenging and identifying interactions between different cells is best obtained through 3D organoid models that reflect the spatial anatomy of a complex structure with greater precision. This ambition is being made possible through my collaboration with the Department of Engineering, Newcastle University Our vision is to engineer human cell based platforms that capture the spatial anatomy of complex multicellular structures thereby facilitating hypothesis-driven identification and functional validation of therapeutic targets disrupting the cancer-niche interplay.
3. Novel drug combination strategies in children’s leukemia
Question: Can we identify targetable niche-mediated synthetic lethal interactors and sensitisors against leukemia dormancy and treatment resistance?
Cancer dormancy and treatment resistance are two key clinical challenges that need urgent attention (Pal D, Heidenreich O, Vormoor J. Dormancy Stems the Tide of Chemotherapy. Cancer Cell, 2016). Using a combined approach of 3D bioprinting and in situ RNA sequencing, my aim is to define cancer-niche communications. We are achieving this objective through our collaboration with Wyss Institute at Harvard. Specifying the functional role of the oncogenic niche in regulating leukemia viability, proliferation, dormancy and treatment resistance will identify novel synthetic lethal interactors of known oncogenes. This will also reveal drug sensitizers in order to tackle treatment resistance, a key clinical challenge. Our vision is to reveal novel “chemo-free” therapeutic strategies towards Phase I trials.
Previous PGR supervision:
1. Miss Sophie Boyd, Newcastle University. MRes 2017. Result: Distinction
2. Miss Sharon Angel, Newcastle University. MRes 2018. Result: Distinction. Won runner up poster prize.
3. Mr. Aaron Wilson, Newcastle university. MRes 2019.
4. Mr. Salem Nizami, Newcastle University [multidisciplinary project cancer research and EPS], MRes 2019
Research Student Supervision Interests1. Regenerative medicine and stem cells, human development/embryology, induced pluripotent stem cell reprogramming 2. 3D tissue engineering and non animal replacement models: organoid models of human bone marrow 3. 3D bioprinting, automated organoid engineering 4. Developing novel therapeutic strategies in children's leukemia, identifying "chemo-free" drug combinations towards Phase I trials 5. Defining the stem cell microenvironment in childhood cancers [paradigm leukemia]
PhD, Genetics, Newcastle University
Regenerative Medicine and Human Development1 Jan 2010 - 14 Jul 2014
MSc, Genetics, Newcaslte University
MBBS, Medicine, Manipal Academy of Higher Education
Fellow (FHEA), Higher Education Academy (HEA)1 Feb 2019 -