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Dr Deepali Pal

Assistant Professor

Department: Applied Sciences

Lab News [follow us on twitter: https://twitter.com/3RsLabPal

Our new podcast: 

https://www.emjreviews.com/oncology/podcasts/battling-childhood-cancer/

Our new research article in F1000 NC3Rs Research Gateway: https://f1000research.com/articles/11-1280/v1 

Read our latest publication in Cell Reports Medicine in finding improved and low toxicity treatments in children's leukaemia using in-house developed New Approach Methodologies: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00260-9

We are very grateful to our funders for supporting our research:

1. NC3RS PhD Studentship award, principal investigator, 2021-2024: £90,000

Project: https://nc3rs.org.uk/our-portfolio/3d-bioprinted-microtissues-develop-patient-specific-non-animal-technologies-nat

2. NC3Rs Fellowship, principal investogator, 2017-2019: £112,473, 

Project: https://www.nc3rs.org.uk/our-portfolio/industrial-standard-cancer-drug-development-platform-using-human-induced-pluripotent

3. Children’s Cancer and Leukaemia Group, The Little Princess Trust Project Grant, principal investigator, 2016-2018: £99,991.60, .

Project: Finding a new drug to treat B-cell acute lymphoblastic leukaemia (ALL) https://www.cclg.org.uk/write/MediaUploads/Research/Impact%20report/415_CCLG-Research-Impact-Report-Download.pdf

4. JGW Patterson Foundation fellowship, principal investigator, 2016-2017: £49,508.27. 

Research Expertise: Cancer research, Malignant bone marrow microenvironment, Regenerative Medicine, Human Development, Stem Cells, Medical Sciences: anatomy, physiology, internal medicine [haematooncology, regenerative medicine and transplant, precision medicine], general surgery [urology, orthopaedics]

Affiliations: Associate Lecturer, Northern Institute for Cancer Research, Newcastle University. 

Biography: 

I am an innovative medical academic specialising in cutting-edge multidisciplinary research that is hypothesis-driven and of significant translational relevance.  My research group focuses on engineering anatomically precise microtissues through 3D bioprinting. Our expertise encompasses stem cells [embryonic/pluripotent stem cells, stem cell reprogramming, mesenchymal stem cells, other adult stem cells], tissue engineering [organoids, 3D biorpinted microtissues] and hypothesis-driven drug combination strategies in leukaemia. We have a specific interest in comparing and contrasting interactions of the bone marrow with leukaemia cells and non-malignant haematopoietic counterparts.

I  have nearly a decade's experience as staff researcher in academia. Following my medical training [Manipal University, India], I obtained an international EU FP7 Marie Curie Fellowship to pursue my doctoral research in human development and regenerative medicine.  Subsequently, in line with my postdoctoral research [JGW Patterson Fellow, MRC-NC3Rs Fellow] I established my group in cancer research and regenerative medicine. Our vision is to deliver clinically relevant non-animal technologies/preclinical models towards regenerative medicine and precision medicine.

Esteem Indicators:

1.EU FP7 Marie Curie Fellow: 2010

2. NC3Rs Fellow: 2017

3. Invited speaker and chair at Kind Philipp Tagung Conference, Wilsede, Germany, 2019

4.Children with Cancer conference, Newcastle, UK, September 2017: Abstract selected as top ten most interesting abstracts for oral presentation. Best talk award at Children with Cancer conference.

5.Association pour la Recherche sur les Tumeurs de la Prostate (ARTP, French Organisation for Prostate Cancer Research) award for the best oral presentation in Prostate Cancer Research at the 20th Meeting of the European Association of Urology Section of Urological Research, Strasbourg, October 2013.

6. 8th NCRI Cancer Conference, Liverpool, November, 2012. Invited speaker. Abstracts won National Cancer Research Institute Prize award 2012.

7. Celebrated female researcher for International Women’s Day, 2018 by NC3Rs: https://www.nc3rs.org.uk/news/celebrating-female-researchers-international-women%E2%80%99s-day-2018

8. Invited speaker on current NC3Rs fellowship as an early-career scientist in the North-East, York University research Symposium, November 2017

 9. Invited by the NC3Rs to write a blog on applying for early career awards, September 2017: https://nc3rs.org.uk/news/applying-early-career-awards  

 10. Invited speaker at Kind Philipp Tagung Conference, Wilsede, Germany, 2017

 11.Invited speaker at European school of Haematology 2nd scientific conference on the tumour environment in haematological malignancies and its therapeutic targeting, Berlin, Germany, 2017

 12. Invited to write a preview article in Cancel Cell [ Journal impact factor: 23.5]

Pal, D., Heidenreich, O., Vormoor, J. Dormancy stems the tide of chemotherapy. Cancer Cell, November 2016

 13. Invited speaker at the CLR-UK meeting, Bristol, 2014: Leukaemia research

 14. Invited speaker at the Academic Urology section of the Annual SARS (Society of Academic and Research Surgery) meeting, 2012.

Lecturing and Scolarship:

I develop and deliver research-led and student-feedback-led lectures in medical and biomedical sciences at undergradutae and postgraduate level. I also provide academic supervision to research students[UG, Masters and doctoral projects].

 

 

Deepali Pal

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

  • Please visit the Pure Research Information Portal for further information
  • Direct targeted therapy for MLL-fusion-driven high-risk acute leukaemias, Cantilena, S., Gasparoli, L., Pal, D., Heidenreich, O., Klusmann, J., Martens, J., Faille, A., Warren, A., Karsa, M., Pandher, R., Somers, K., Williams, O., de Boer, J. Jun 2022, In: Clinical and Translational Medicine
  • Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia, Tirtakusuma, R., Szoltysek, K., Milne, P., Grinev, V., Ptasinska, A., Chin, P., Meyer, C., Nakjang, S., Hehir-Kwa, J., Williamson, D., Cauchy, P., Keane, P., Assi, S., Ashtiani, M., Kellaway, S., Imperato, M., Vogiatzi, F., Schweighart-James, E., Lin, S., Wunderlich, M., Stutterheim, J., Komkov, A., Zerkalenkova, E., Evans, P., McNeill, H., Elder, A., Martínez-Soria, N., Fordham, S., Shi, Y., Russell, L., Pal, D., Smith, A., Kingsbury, Z., Becq, J., Eckert, C., Haas, O., Carey, P., Bailey, S., Skinner, R., Miakova, N., Collin, M., Bigley, V., Haniffa, M., Marschalek, R., Harrison, C., Cargo, C., Schewe, D., Olshanskaya, Y., Thirman, M., Cockerill, P., Pal, D. 27 Oct 2022, In: Blood
  • hiPSC-derived bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukemia, Pal, D., Blair, H., Parker, J., Hockney, S., Beckett, M., Singh, M., Tirtakusuma, R., Nelson, R., McNeill, H., Angel, S., Wilson, A., Nizami, S., Nakjang, S., Sankar, S., Zhou, P., Schwab, C., Sinclair, P., Russell, L., Coxhead, J., Halsey, C., Allan, J., Harrison, C., Moorman, A., Olaf, H., Vormoor, J. 16 Aug 2022, In: Cell Reports Medicine
  • Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL, Molina, O., Vinyoles, M., Granada, I., Roca-Ho, H., Gutierrez-Agüera, F., Valledor, L., López-López, C., Rodríguez-González, P., Trincado, J., Tirados-Menéndez, S., Pal, D., Ballerini, P., Den Boer, M., Plensa, I., Perez-Iribarne, M., Rodriguez-Perales, S., Calasanz, M., Ramírez, M., Rodríguez, R., Camos, M., Calvo, M., Bueno, C., Menendez, P. 16 Jul 2020, In: Blood
  • Reactive jet impingement bioprinting of high cell density gels for bone microtissue fabrication, da Conceicao Ribeiro, R., Pal, D., Ferreira, A., Gentile, P., Benning, M., Dalgarno, K. 1 Jan 2019, In: Biofabrication
  • Targeting the thioredoxin system as a novel strategy against B-cell acute lymphoblastic leukemia, Fidyt, K., Pastorczak, A., Goral, A., Szczygiel, K., Fendler, W., Muchowicz, A., Bartlomiejczyk, M., Madzio, J., Cyran, J., Graczyk-Jarzynka, A., Jansen, E., Patkowska, E., Lech-Maranda, E., Pal, D., Blair, H., Burdzinska, A., Pedzisz, P., Glodkowska-Mrowka, E., Demkow, U., Gawle-Krawczyk, K., Matysiak, M., Winiarska, M., Juszczynski, P., Mlynarski, W., Heidenreich, O., Golab, J., Firczuk, M. May 2019, In: Molecular Oncology
  • Differentiation of Human Embryonic Stem Cells to Sympathetic Neurons: A Potential Model for Understanding Neuroblastoma Pathogenesis, Carr-Wilkinson, J., Prathalingam, N., Pal, D., Moad, M., Lee, N., Sundaresh, A., Forgham, H., James, P., Herbert, M., Lako, M., Tweddle, D. 1 Nov 2018, In: Stem Cells International
  • Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase, Fordham, S., Blair, H., Elstob, C., Plummer, R., Drew, Y., Curtin, N., Heidenreich, O., Pal, D., Jamieson, D., Park, C., Pollard, J., Fields, S., Milne, P., Jackson, G., Marr, H., Menne, T., Jones, G., Allan, J. 22 May 2018, In: Blood
  • The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation, Martinez-Soria, N., McKenzie, L., Draper, J., Ptasinska, A., Issa, H., Potluri, S., Blair, H., Pickin, A., Isa, A., Chin, P., Tirtakusuma, R., Coleman, D., Nakjang, S., Assi, S., Forster, V., Reza, M., Law, E., Berry, P., Mueller, D., Elder, A., Bomken, S., Pal, D., Allan, J., Veal, G., Cockerill, P., Wichmann, C., Vormoor, J., Lacaud, G., Bonifer, C., Heidenreich, O. 8 Oct 2018, In: Cancer Cell
  • Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia, Elder, A., Bomken, S., Wilson, I., Blair, H., Cockell, S., Ponthan, F., Dormon, K., Pal, D., Heidenreich, O., Vormoor, J. Dec 2017, In: Leukemia

  • Sean Hockney 3D Bioprinted Microtissues to Develop Patient-specific Non-animal Technologies in Cancer Drug Development Start Date: 01/10/2021
  • Jessica Parker Clinically relevant mini-organs to identify optimal ‘chemo’-free treatments for childhood cancer Phase I trials Start Date: 18/01/2021

  • Genetics PhD July 14 2014
  • Genetics MSc December 31 2009
  • Medicine MBBS April 30 2008
  • Fellow (FHEA) Higher Education Academy (HEA) 2019


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