पेंशनर्स कॉर्नर
स्क्रीन रीडर एक्सेस
मुख्य सामग्री पर जाएं
CSIR-DAAD
Call Ref. No. E6666: AB-CSIR/1159/2022-ISTAD-CSIR HQ dated 10/07/2024Bilateral Exchanges of Scientists/Academics - 2024
Application form for CSIR Scientist for Visiting Germany
Application Reference No. : CSIR-DAAD/2024/
Date of Submission :
Date of Submission :
- 1) Name Dr. Shruthy Suresh Aggarwal
- 2) Designation (Present) Scientist
- 3) Lab/Inst. CSIR-Institute of Genomics and Integrative Biology(CSIR-IGIB), Delhi
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4) Area of Research
cancer biology
molecular biology
cancer metastasis - 5 (i)) Date of Birth 04-02-1992
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5 (ii)) Age
Year32Month6
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6) Date Of Joining CSIR With Designation
Date of Joining CSIR2023-10-25Designation (At the time of joining CSIR)Scientist
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7) Qualification
,DegreePhDBoard / UniversityUniversity of Texas Southwestern Medical CenterDivisionMolecular BiologySubjectCancer BiologyYear2019DegreeB.TechBoard / UniversityIndian Institute of Technology MadrasDivisionBiotechnologySubjectBiotechnologyYear2013
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8) Knowledge of foreign languages
LanguageGerman but very basic levelSelect LanguageCan Speak
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9) Experience
Position HeldPostdoctoral Research FellowDurationFrom2020-01-06To2022-11-30Nature of Work (in 10 words)identification of metastasis modulators using human patient samples and CRISPR Cas9
- 10) Number Of Publications
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11 (i)) Number Of Patents
National0International0
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11 (i)) Number Of Book/Book Chapter
National0International2
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12) Awards & Recognition
National1. INSPIRE FACULTY FELLOWSHIP 2022 - Department of Science & Technology, India
2. Khorana Scholars Program 2012 - Department of Biotechnology, India
3. IIT-JEE All India Rank 3244
4. AIEEE All India Rank 2987 and State Rank 72
International1. Melanoma Research Foundation Career Development Award 2020 - Melanoma Research Foundation, USA
2. Translational Research in Oncology Training Fellowship 2020 - Memorial Sloan Kettering Cancer Center, New York, USA
3. Best Student Talk Travel Award in 2019, Simmons Comprehensive Cancer Center, Texas, USA
4. Best Student Poster Travel Award in 2015 and 2017, Simmons Comprehensive Cancer Center, Texas, USA
5. Runner-up best Poster Prize, 2019, Invivo Metabolism Conference, Dallas, Texas, USA
6. Clinical to Grad Fellowship, 2014, Howard Hughes Medical Institute, USA
7. Cancer prevention research Institute of Texas Training Grant, 2017, CPRIT, Texas, USA
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13) List tangible acheivements in terms of Research, Development and Innovation Output of the Candidate (max upto 10)
Research Output:
1. My PhD thesis along with others' work has led to the testing of ISR inhibitors in Phase 2 clinical trials for lung cancer in USA.
2. Number of high impact publications: 14 , including in prestigious journals such as SCIENCE and CANCER DISCOVERY.
3. My PhD Thesis work contributed to the lab being awarded several grants: Welch Foundation 2018, Friends of Comprehensive Cancer Center Award 2017, NCI SPORE Award 2016
4. Awarded multiple prestigious grants as Principal Investigator or training grant till date amounting to total of ~3.5 crore INR
5. Mentored 7 PhD students during my PhD & postdoc, currently a thesis advisor for 3 PhD students and a DAC member for 7 PhD students at CSIR-IGIB
6. Led 6 projects as a PhD and postdoc and contributed to 10+ projects in collaborative manner. As scientist at IGIB, I am currently running 4 different projects.
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14) Major achievements/contribution of international level in the proposed area of research (In approx. 250 words)
The curiosity to understand cancer as a disease has been a unifying theme across various stages of my scientific journey. During my B.Tech at IIT Madras, I worked on Menadione as an anti-cancer agent, resulting in two publications from my thesis. As a PhD student, in a landmark study, I performed a genome-wide CRISPR knockout screen to identify regulators of PD-L1 in human lung cancer and uncovered a novel translational regulation of PD-L1 mRNA triggered by activation of Integrated Stress (ISR) Response in human lung cancer (Suresh et al, Nature Cancer (IF 23) 2020). This study along with others have demonstrated a critical role for ISR in tumorigenesis. Importantly, my work had direct clinical impact- ISR inhibitors currently in clinical trials for human lung adenocarcinoma.
As a postdoc, to identify novel modulators of metastasis, I collaborated with the Sanger Institute, UK and performed RNASeq on primary tumors from melanoma patients who went on to metastasize vs who did not. I identified GRAMD1B as a novel metastasis suppressor in melanoma (Suresh et al, Cancer Discovery, 2023 (IF 39)). I was awarded the Melanoma Research Foundation Career Development Award and MSKCC TROT fellowship 2020 for this work. My work has contributed to several studies in the White Lab (Baggiolini, Science 2021 (IF 47.71), Tagore et al, Cancer Discovery 2023 (IF 39)).
My work in cancer biology has garnered recognition in the scientific community at the national and global level, through grants, awards and high-impact publications, demonstrating my expertise in this domain.
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15) Name of the host Professor / Guide and full address of the Foreign Instt / Univ / R&D lab (In approx. 250 words)
Professor Ulf Kahlert,
Clinic for Surgery, Medical Faculty, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. - 16) Research accomplishments of the host (In approx. 250 words) Dr. Kahlert has attracted a total of over 2.2 M EUR research funding. And published over 95 peer reviewed scientific papers, including high impact papers such as Nature communications, Cell Metabolism, Cell Death Discovery etc. Dr. Ulf Kahlert is an expert in analyze patient data and generating high risk gene signatures that predict cancer prognosis (Zhang et al, 2024, Hu et al 2023 among others). Dr. Kahlert's group also has excellent expertise in the generation and maintainence of biobank of patient tumor and matched normal tissues and developing patiend derived organoids from them. He leads the MES as a Director and is managing the nanodelivery teams, robotic surgery in cancer as well as the wet labs that do cancer research at MES. He has also won many awards, 2014 Outstanding abstract in “Translational Science” Johns Hopkins Young Investigator Day in Pathology, Baltimore, MD, USA 03/2013 Dr. Mildred-Scheel Postdoctoral Fellowship by the German Cancer Aid to name a few.
- 17) Major research facilities at the host laboratory/institute (In approx. 250 words) The MES Core Laboratory Unit consists of 220 sqm state of the art biosafety lab facilities with separated office spaces. It consists of two separate cell culture suites (primary culture, clean culture room), two molecular labs, bio bank room with freezing equipment, cool room and analytics room. The Histology Core Unit – equipped with a digital pathology system including sectioning and tissue embedding stations – as well as time-lapse microscopy and FACS sorter and FACS analyzer are available. Basic molecular biology equipment such as centrifuges, PCR machines, thermomixers, sonicators are also available.
- 18) Prior linkage/cooperation with the host (In approx. 250 words) There is an ongoing MoU in the process between CSIR-IGIB and MES, University of Magdeburg, which the host is involved in. CSIR-IGIB, and MES endorse the establishment of collaboration between the two institutes through signing of this MoU to facilitate scientific interactions in the domain areas of Life Sciences, Genomics and Human Disease Biology, working on joint projects and the exchange of ideas, students, trainees between the two institutes.
- 19) Reasons for selecting the proposed host (In approx. 250 words) Dr. Ulf Kahlert is an expert in analyze patient data and generating high risk gene signatures that predict cancer prognosis (Zhang et al, 2024, Hu et al 2023 among others). Dr. Kahlert's group also has excellent expertise in the generation and maintainence of biobank of patient tumor and matched normal tissues and developing patiend derived organoids from them. As a oncological colon cancer center and oncological pancreas cancer center as certified by the German Cancer Society, with approximately 2 tumor operations per day, they efficiently collect, preserve, characterize and process patient specimens.
- 20) Title of the research proposal to be carried out abroad Identification of genes that confer immunotherapy resistance in hepatocellular carcinoma
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21) Abstract of the Research Proposal (max 500 words)
Liver cancer is the fourth leading cause of cancer-associated deaths worldwide. Hepatocellular carcinoma (HCC), the cancer of hepatocytes, accounts for over 80% of liver cancers. The incidence of HCC is on the rise in India, with reported incidence rates of 50-80,000 cases annually [1]. Risk factors for HCC include Hepatitis B and C virus infection (HBV, HBC), alcohol use, cirrhosis, smoking, diabetes and obesity. A majority of HCC cases in India are diagnosed in advanced stages, with patients displaying multi-focal hepatic tumor nodules and intra-hepatic metastasis. These tumors are treated with systemic chemotherapy, radiation or liver transplantation, but are rarely curable [1]. A lack of targeted therapies against advanced HCC portends poor survival of HCC patients in India, with a high ratio of mortality to incidence (0.95) [1].
Genomic analyses of HCC patient tumor tissues have been a powerful approach to identify new therapies in HCC. These studies have identified important driver mutations such as MYC, TP53, CCND1, CTNNB1, but few are translated to the bedside as they are either not druggable or present at lower frequencies [2]. Currently, HCC patients receive systemic therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors, which prolongs patient survival by a few months [2]. Of note, immune therapy successes in many solid tumors can be predicted by markers such as PD-L1 status or MMR/MSI status, which is not indicative in HCC. Given the high costs of immunotherapy, the identification of powerful predictors indicating vulnerability is not only of clinical need but also high economic need [6]. Large scale analysis of patient samples as well as studies in mice models have identified several candidate genes that may play a role in predicting and driving response to immunotherapy. However, to the best of our knowledge, very few studies have functionally validated the role of these candidates in driving immune resistance. Furthermore, it is increasingly appreciated that functional validation of target genes in primary patient-derived organoids or stem cell models can have high clinical predictive value [7,8]. Additionally, the development of sophisticated patient derived organoids that can model the tumor microenvironment (TME) can serve as a welcome alternative to animal modelling of cancer.
In this study, we propose to establish immune competent autologous patient-derived organoid (PDO) model systems of HCC and corresponding healthy tissue control. Secondly, we will utilize a list of putative candidate genes that are clinically associated with immune resistance in HCC. Clinical informatics will be performed in published HCC patient datasets as well as biomaterial obtained from HCC patients in University of Magdeburg Medical Hospital to assess if altered expression of these genes is clinically associated with disease prognosis, response to immune checkpoint blockade and patient survival. We will then functionally interrogate the role of these genes in immune resistance through pooled CRISPR screening in HCC PDOs. We anticipate that this study will establish robust PDO models to study tumor-TME interaction in HCC and identify novel therapeutic avenues to reverse immune resistance in HCC.
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22) Please give 500 words write-up on the novelty of the research topic
Liver cancer is the fourth leading cause of cancer-associated deaths worldwide. Hepatocellular carcinoma (HCC), the cancer of hepatocytes, accounts for over 80% of liver cancers. The incidence of HCC is on the rise in India, with reported incidence rates of 50-80,000 cases annually. Currently, HCC patients receive systemic therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors, which prolongs patient survival by a few months [2]. Of note, immune therapy successes in many solid tumors can be predicted by markers such as PD-L1 status or MMR/MSI status, which is not indicative in HCC. Given the high costs of immunotherapy, the identification of powerful predictors indicating vulnerability is not only of clinical need but also high economic need. Till date, while studies have identified genes associated with immunotherapy resistance, causal association and functional interrogation of the same is lacking. There is a pressing need to identify and understand why some tumors respond to ICB vs some do not. This is precisely the question our project tackles on in this proposal.
In this study, we propose to establish novel immune competent autologous patient-derived organoid (PDO) model systems of HCC and corresponding healthy tissue control. This work is novel for many reasons – PDOs are a new, emerging technology in the last decade that has been used to study a range of human diseases. PDO-immune co-culture system where immune cells are derived from the patient blood is a powerful and physiologically relevant system to interrogate tumor microenvironment interactions without the use of animal models, and is likely applicable to many tumor types. We will combine this novel system with a focused CRISPR library generation and CRISPR based pooled screening for regulators of immune therapy resistance in HCC. To our knowledge, a study of this type has not been performed in liver cancer. We anticipate that this study will establish robust PDO models to study tumor-TME interaction in HCC and identify novel therapeutic avenues to reverse immune resistance in HCC.
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23) Explain allignment/Relevance of the proposed work with priority Themes/Projects/Programmes of Lab/CSIR (In approx. 250 words)
The proposed work entails using patient biobank samples and molecular biology and modelling approaches to identify new vulnerabilities in human cancer, particularly in liver cancer. Liver cancer is a disease of great burden in India and worldwide. The incidence of HCC is on the rise in India, with reported incidence rates of 50-80,000 cases annually. A majority of HCC cases in India are diagnosed in advanced stages, with patients displaying multi-focal hepatic tumor nodules and intra-hepatic metastasis. These tumors are treated with systemic chemotherapy, radiation or liver transplantation, but are rarely curable. A lack of targeted therapies against advanced HCC portends poor survival of HCC patients in India, with a high ratio of mortality to incidence (0.95). Thus, there is a critical unmet need in understanding new regulators of HCC progression.
CSIR has been a leader in addressing these knowledge gaps in cancer biology with the goal to identify new therapeutic targets for cancer treatment. CSIR has a running Pan-Cancer program to understand Indian cancer patient biology and develop new biomarkers. There is also an interest from CSIR (Mission Mode) for CAR-T development in cancer. Thus, cancer as a human disease is an ongoing high priority theme at CSIR. This makes our proposal fit with the needs of CSIR and its priority areas of pursuit for research.
- 24(i)) Does the proposed research work involve IPR issues. No
- 24(ii)) Has the host institute agreed to share the same with CSIR?
- 25) Could the proposed work be carried out within India at CSIR/non CSIR S&T institutions? (Please justify the need to conduct it in the proposed foreign institution in 500 words.) The MES led by Dr. Ulf Kahlert is the Director of the MES at University of Magdeburg. The MES is a pioneer in developing patient biobank of tumor tissues and matched normal tissues in gastrointestinal cancers such as liver, colon and pancreatic cancer. s a oncological colon cancer center and oncological pancreas cancer center as certified by the German Cancer Society, with approximately 2 tumor operations per day, we efficiently collect, preserve, characterize and process patient specimens. The availability of high quality, well characterized biomaterial which can be subjected to various molecular and/or cellular procedures, alongside with the access to associated patient-individual metadata such as clinical records and imaging data, allows for highly relevant reverse translational research. The reliable and long-term clinical followup of patients is a very unique aspect of MES. Furthermore, Dr. Kahlert's group also has expertise in the development of patient derived organoids (PDO) from the tissues isolated in the Biobank with new cases everyday. The MES has infrastructure to maintain a robust biobank, generate PDO from these for molecular analyses and perform clinical covariate analysis on tumor samples from these patients, the combination of which is compelling, cutting-edge, competitive and not possible to find in existing institutions in India.
- 26) Minimum period required for conducting proposed research. (14 days – 3 months) 3-4 weeks
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27) Nature of expected output from the proposed study and its likely uses (In approx. 250 words)
We anticipate that the major outputs would be in domains of technology development, knowledge transfer and identification of drugs for preclinical testing for cancer.
In terms of technology development, the PDO-immune co-culture system that utilizes organoids dervied from patients and stimulated immune cells derived from the same patient is a novel and powerful system that is physiologically relevant and applicable and scalable to many tumor types. This is thus a valuable technology development from this project.
In terms of knowledge transfer, this would be a very useful resource to all cancer biologists in India. and a great transfer of knowledge from Germany to India.
In terms of target identification, we anticipate that our pooled CRISPR screen will identify new pharmacologically targetable proteins that can then be combined with immunotherapy to assess if it boosts tumor killing in preclinical models.
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28) Benefits to CSIR (In approx. 250 words)
CSIR would benefit from this work in the domains of technology development, knowledge transfer and identification of drugs for preclinical testing for cancer.
In terms of technology development, the PDO-immune co-culture system that utilizes organoids dervied from patients and stimulated immune cells derived from the same patient is a novel and powerful system that is physiologically relevant and applicable and scalable to many tumor types. This is thus a valuable technology development from this project.
In terms of knowledge transfer, this would be a very useful resource to all cancer biologists in India. and a great transfer of knowledge from Germany to CSIR.
In terms of target identification, we anticipate that our pooled CRISPR screen will identify new pharmacologically targetable proteins that can then be combined with immunotherapy to assess if it boosts tumor killing in preclinical models. This will likely lead to a hit with translational potential and clinical impact.
- 29) Commercialisation prospects of the proposed research work (In approx. 250 words) If the candidate hits from our studies are targetable, pharmacological inhibition of these targets will be undertaken in combination with immunotherapy to assess if it boosts tumor killing in PDOs and animal models. If this pans out, then emerges a commercialization aspect.
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30) PREVIOUS VISITS ABROAD DURING LAST 3 YEARS
,CountryUnited States of AmericaYear2022Purpose With DetailsPostdoctoral Research Fellowship at Memorial Sloan Kettering Cancer Center, USADuration of Visit2 years 11 months (2020-2022),CountryMaldivesYear2024Purpose With DetailsFamily personal vacationDuration of Visit4 daysCountryUnited KingdomYear2022Purpose With DetailsSociety for Melanoma Research Conference at Edinburg, Scotland, UKDuration of Visit10 days
- 31) Any other relevant information you may feel necessary to give N/A
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For CSIR candidates :
1) Curriculum VitaeSuresh_CV_2024_3Pg_final.pdf (163.18 किलोबाइट)3) Research ProjectCSIR_DAAD_ResearchProject_SSA.pdf (295.21 किलोबाइट)4) Time Plan/Itinerary of VisitTimePlanOfVisit.pdf (121.9 किलोबाइट)5) Confirmation/acceptance from the German hostLetter of Consent Shruty Aggarwal.pdf (267.75 किलोबाइट)6) Specific Recommendations of the Director of the CSIR InstituteSpecific_Recommendation_Director.pdf (572.03 किलोबाइट)2) Publications/Patents/Book/Book Chapter (in Tabular Format)Publications_Tabular_SSA_0.pdf (176.59 किलोबाइट)
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For German Candidates :
1) Curriculum VitaeCV_Ulf.pdf (181.08 किलोबाइट)2) Publications/Patents/Book/Book Chapter (in Tabular Format)Literaturliste komplett 08_24.pdf (379.15 किलोबाइट)7) Nomination form for the German candidate recommended by the Director (As per annexure II))Annexure_German_DirectorApproval final.pdf (388.84 किलोबाइट)8) Written acceptance letter of the German candidateLetter of Consent Shruty Aggarwal_0.pdf (267.75 किलोबाइट)9) A detailed Itinerary of visitTimePlanOfVisit_0.pdf (121.9 किलोबाइट)
