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Dr Deepali Pal

Assistant Professor

Department: Applied Sciences

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

Our new publication showing development of human-cell-based MSC-ALL spheroid models with high in vivo predictivity :  A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing

Active projects, externally funded:

3D bioprinted microtissues to develop patient-specific non-animal technologies (NAT) in cancer drug development

Assessment of an in vitro acute lymphoblastic leukaemia model for high-throughput arrayed CRISPR screening  Utilising the technology developed by Dr Deepali Pal, this project was awarded £42,268, aiming to identify gene pathways by which leukaemia cells interact with bone marrow cells, and how these interactions might contribute to drug resistance. 

Key Discovery: 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 T2T scheme, academic principal investigator, 2023-2024

Project: Assessment of an in vitro acute lymphoblastic leukaemia model for high-throughput arrayed CRISPR screening 

3. 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

4. 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

5. 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: 

My vision is to develop safer and kinder, chemotherapy-free and biology-driven treatments for childhood leukaemia.

My research strategy is to integrate basic biology and translational research with engineering and physical sciences, and develop transformative research technologies and preclinical models, to drive breakthrough discoveries that postively impact patient outcome.

I have two research goals: 1. Discovery of new mechanisms and cell-cell crosstalk that drive cancer biology within the context of its microenvironment, and consequently discovery of clinically actionable targets in childhood leukaemia 2. Development of transformative research technologies, preclinical models and methods to enable clinically relevant research and breakthrough biological discoveries.

I lead an interdisciplinary research group driving hypothesis-driven projects of significant translational relevance.  My research group focuses on engineering anatomically precise and clinically relevant microtissues through 3D bioprinting. Our expertise encompasses stem cells [induced pluripotent stem cells, stem cell reprogramming, mesenchymal stem cells, other adult stem cells], tissue engineering [organoids, 3D biorpinted microtissues], exploring mechanistics of cancer-microenviornment interactions and hypothesis-driven target discovery identifying novel drug combination strategies in leukaemia. 

I  have over 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 mentor early career researchers and supervise doctoral students. I develop and deliver research-led and student-feedback-led modules and lectures in medical and biomedical sciences. 

 

 

Deepali Pal

We are keen on hearing from driven and conscientious PhD candidates. We provide mentorship to early career researchers 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?

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?

Developing a scalable, tractable, 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. Using transformative 3D bioprinted co-culture organoid models, my aim is to define cancer-niche communications. 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.

 

  • Please visit the Pure Research Information Portal for further information
  • Susceptibility of pediatric acute lymphoblastic leukemia to STAT3 inhibition depends on p53 induction, Gasparoli, L., Virely, C., Tsakaneli, A., Che, N., Edwards, D., Bartram, J., Hubank, M., Pal, D., Heidenreich, O., Martens, J., de Boer, J., Williams, O. 31 Mar 2024, In: Haematologica
  • A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing, Wilson, A., Hockney, S., Parker, J., Angel, S., Blair, H., Pal, D. 6 Nov 2023, In: F1000Research
  • Next generation organoid engineering to replace animals in cancer drug testing, Hockney, S., Parker, J., Turner, J., Todd, X., Todryk, S., Ger Gieling, R., Hilgen, G., Camargo Madeira Simoes, D., Pal, D. 1 Jul 2023, In: Biochemical Pharmacology
  • Targeting N-Cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia, Parker, J., Hockney, S., Blaschuk, O., Pal, D. 3 May 2023, In: Expert Reviews in Molecular Medicine
  • 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. 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

  • 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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