I am an early career cancer researcher and a Newton International Fellow of Academy of Medical Sciences (one of only nine in the UK in 2019). I was also successful in securing the Research England/Global Challenges Research Fund (GCRF) support and the H2020 Marie Sklodowska-Curie Actions Seal of Excellence Award. These awards were despite a non-standard academic career pathway (e.g., several research career breaks etc.) as I have deep passion for science, robust work ethics and flexibility. With this spirit, I have 6.3-years of post-PhD actual research experience (till August 2024) that brings me where I am now (underlined as an executive summary below) and from here I want to go beyond. 

Executive Summary: 

• Early Career Translational Cancer Researcher with h-index 13
• Delivered 6 projects by acquiring grant value of ~£153,500
• Newton International Fellow of Academy of Medical Sciences (2019 -2022) and Union for International Cancer Control (UICC) Fellow (2017)  
• Invited speaker at the European Society for Radiotherapy and Oncology (ESTRO) congress in 2020
• Ambassador of European Association for Cancer Research (EACR) and life member of UICC
• Reviewer of grants (UICC & Swiss 3RCC) and research articles (Biology Open & Discover Oncology)
• Collaborator of clinicians and academicians and public speaker (https://doi.org/10.1242/bio.059987 )

I have a considerable research experience in cancer biology with in-vivo [e.g., patient-derived xenograft (PDX)], ex-vivo (e.g., PDX co-culture) and in vitro (e.g., 2D and 3D cell culture) models. I hold the Home Office license PIL A/B (ID3B2DFC3) and PIL C training to work with mice. Besides my wet lab experience, I have professional training in computer programming languages and data analysis tools extensively used in Bioinformatics (e.g., R and Python). I am also an expert in using publicly available Bioinformatics tools like: GEPIA2, UALCAN, GSCA: Gene Set Cancer Analysis, TIMER: Tumour Immune Estimation Resource, Templo, GENE-E, STRING, Connectivity Map (CMAP), cBioPortal for Cancer Genomics::Datasets, National Cancer Institute (NCI)'s Genomic Data Commons (GDC). Thus, I am uniquely placed to explore wet lab and dry lab research skills to extend my cancer research. To conduct my pioneering research, I will be building a team and for that, I am collaborating with the expert researchers all around the world. My future research is focused on the following area with summary.  

• Translational Cancer Research (Head and Neck Cancer and Blood Cancer)
• Radiation Oncology
• Tumour Hypoxia
• Onco-nephrology
• High-throughput drug screening and gene-drug corelation

Radiation Oncology and Tumour Hypoxia:

In my Newton International Fellowship, I have worked with an inhibitor of DNA damage response protein poly-ADP ribose polymerase (PARP) named Rucaparib, discovered in my Newcastle lab. My research was the first to show that Rucaparib can potentiate cervical cancer cell killing in combination with cisplatin and radiotherapy (RT) plus protect kidneys from the cisplatin-induced acute kidney injury (AKI) (PMID: 36077823). My research has direct benefit to the Head and Neck Cancer (HNC) patients as the cisplatin-induced AKI is very common in HNC as well. This pioneering research drives my motivation to explore the consequences of RT-induced toxicity in immune cells, a promising and developing field for cancer therapeutics. To explore that, I have established an innovative tool by growing HNC tumour cells with components of the immune cells in the petri-dish to mimic complex tumour microenvironment and called it “tumouroid” (PMID: 37194999). Exploiting this state-of-the-art tool, I aim to discover novel radio - immunotherapy combination to benefit HNC patients. My long-term goal is to exploit my tumoroid tool with more advanced RT approaches like Proton Beam Radiotherapy/FLASH radiotherapy to discover more effective anticancer treatment. In expansion of this study, I will look at the immunosuppressive role of the hypoxic cells as hypoxic tumours are resistance of any therapy and there is no hypoxia-targeting drug in the clinic. I (PMID: 37194999) and other researchers have observed that tumouroids are the ideal model to recapitulate hypoxic tumours in vitro and very little is known about hypoxia-induced immune suppression. Thus, I will explore my tumouroid tool to explore this novel research and my overall objectives in this area are:

(1) to discover small molecule as novel radiosensitiser

(2) to test small molecule – RT combination induced inflammatory responses

(3) to discover novel radio-immunotherapy combination exploring radio-genomics

(4) delve the mechanism of hypoxia-induced immune suppression

(5) discover novel hypoxia targeting drug(s) and biomarker(s)

Onco-nephrology:

Head and neck cancer (HNC) is the 3rd fastest growing cancer in the UK. HNC patients are often socioeconomically deprived and are smokers with high alcohol intake, contributing to poor kidney function. HNC patients are treated with a drug called cisplatin and radiotherapy, this is the most effective therapy. However, cisplatin causes acute (or rapid) kidney injury (AKI) in 70% HNC patients and treatment is discontinued. For patients >70 years and those with poor kidney function, cisplatin cannot be given, because of AKI. Unfortunately, there is no medicine to protect kidneys from the cisplatin-induced AKI.

I observed cisplatin causes tissue damage, driving inflammation and triggering AKI. I discovered that cisplatin-induced AKI is partly due to a protein called PARP and inhibition of PARP by rucaparib (a drug) partially protects the kidneys. It is also clear that cisplatin still activates many other negative pathways.

The complement system (part of our immune system) drives inflammation in damaged kidneys. Factor H (FH) regulates the complement system. A therapy named homodimerised minimal FH (HDM-FH) has been developed in Newcastle University to prevent kidney inflammation. However, role of anti-complement or anti-inflammatory therapies to protect kidneys from the cisplatin toxicity is very less known and I want to explore that novel area. Knowledge from this research I want to explore in many other cancer types where other anti-cancer druugs like cisplatin has adverse side effects to the kidneys. Thus, objectives of my future research in this area are:

(1) to test if HDM-FH can reduce cisplatin-induced AKI

(2) Discover which other inflammatory molecules are overexpressed in cisplatin-induced AKI.

(3) Can HDM-FH protect from cisplatin-induced chronic kidney injury (CKI)

(4) Can HDM-FH protect the kidneys while cisplatin ± radiotherapy (RT) kill HNC xenograft tumours

(5) Identifying a robust biomarker of kidney function in HNC

(6) test FDA-approved drug libraries/anti-inflammatory medicines to enhance killing of in vitro HNC cells, while remaining non- toxic to urine-derived renal epithelial organoids

High-throughput drug screening and gene-drug corelation:

In my current research, I am evaluating ex vivo cytotoxicity of ~2000 FDA-approved drugs and co-relating the drug-sensitivity data with the genomic profile to discover a novel therapy in a subtype of childhood blood cancer with intrachromosomal amplification of chromosome 21 (iAMP21). For this, I am exploring high-throughput microscopy, Machine Learning approach to analyse microscopic images and Bioinformatics skills to find the gene-drug association. Alongside, I have also achieved the Welcome Trust Translational Partnership (WTTP) Translational Explorer grant to develop my bioinformatics skill as mentioned above. To follow-on, the work driven by this project my vision is to explore “The immune landscape of iAMP21 blood cancer”. The aim is to explore the genomic profile to outline the Immune signatures that will predict the treatment with novel immunotherapy, which is an innovative and promising treatment approach in cancer.

Head and Neck Cancer (HNC) clinicians:

1. Dr Charles Kelly - HNC clinician @ The Newcastle upon Tyne Hospitals, UK
2. Dr Iain Nixon - HNC clinician @ University of Edinburgh/NHS Lothian, UK
3. Professor Keith Hunter - HNC clinician @ University of Liverpool, UK

Head and Neck Cancer (HNC) and Radiation researchers:

1. Dr. Gabrielle Grundy- HNC researcher with focus on radiotherapy @ University of Liverpool, UK
2. Professor Kaye Williams - combination radiotherapy researcher @ University of Manchester, UK
3. Professor Anna Dubrovska - HNC researcher with focus on radiotherapy @ OncoRay, Germany

Blood Cancer researcher:

1. Professor Christine Harrison @ Newcastle University, UK

Immunologists and Kidney researcher:

1. Professor Kevin J. Marchbank – Immunologist and kidney researcher (involved in cancer research, i.e., liver cancer), key collaborator and mentor @ Newcastle University, UK.
2. Professor Jacques Neefes - Chemical Immunologist @ Leiden University, Netherlands.

Organoid researcher:

1. Professor Hans Clevers Hubrecht - Organoid Researcher @ University, Netherlands

2022 (£5,580)

• Wellcome Trust Translational Partnership (WTTP) Translational Explorer Grant

Establishing the drug-gene association matrix pipeline of childhood leukaemia.

Santu Saha (lead applicant), Christine Harrison (co-applicant/mentor).

2021 (£10,000)

• Wellcome Trust Translational Partnership (WTTP) Early Translational Research Grant

Establish 3D-spheroid co-culture model to investigate the immunomodulatory impact of PARP inhibitor (PARPi) and radiotherapy combination in Head and neck cancer.

Santu Saha (lead applicant), Nicola Curtin (co-applicant), Charles Kelly (co-applicant and clinical collaborator).

2019 (£99,000)

• Newton International Fellowship of Academy of Medical Sciences

Investigating therapeutic application of PARP inhibitor as chemo-radiosensitser in cervical cancer and its effect on renal protection.

Santu Saha (lead applicant), Nicola Curtin (co-applicant/mentor).

2019 (£20,000)

• Research England Global Challenges Research Fund (GCRF) Quality Related (QR) research support

Newcastle University Faculty of Medical Sciences ‘strategic initiative’ support to the Newton International project as the project matches the merit of Official Development Assistance (ODA). 

Santu Saha (lead applicant) and Nicola Curtin (co-applicant/mentor).

2019 (€2,300/~£2000)

• European Society for Radiotherapy and Oncology (ESTRO)

The effect of PARPi on therapy resistance of cervical cancer stem cells.

Santu Saha (lead applicant) and Anna Dubrovska (co-applicant and academic collaborator at OncoRay, Dresden, Germany).

2017 ($3,400/ ~£3000)

• The Union for International Cancer Control (UICC) Technical Fellowship

Investigating radiosensitisation in cervical cancer using DNA damage response pathway inhibitors.

Santu Saha (lead applicant) and Nicola Curtin (co-applicant/mentor).

2015 (GRANT: ₹12,54400/ ~ £12,544)

• Department of Biotechnology (DBT), India

Analysis of Hyaluronan-CD44 mediated signalling in head and neck squamous cell carcinoma.

Santu Saha (lead applicant) and Chinmay Panda (co-applicant/mentor).

Module Leader:

Proteomic Technologies (SCI4076-N)

Module Tutor:

Python for Bioinformatics (SCI4077-N)

Clinical Genetics (SCI3045)

Molecular Biology and Bioinformatics (SCI2008)

Advanced/Applied Practice in Health & Life Sciences (SCI4039)

Life Science Project (SCI4013)

Grant Reviewer

• The Union for International Cancer Control (UICC)
• Swiss 3RCC

Paper Reviewer

• Biology Open
• Discover Oncology