Funding Opportunities

Precision Medicine RFP's

Proposals are requested for one-year pilot studies in precision medicine. Studies must be relevant to advancing precision medicine basic science, pre-clinical/clinical approaches to tailoring medical care (prevention, diagnosis, and/or treatment) to the individual patient, and/or precision cancer research.

Example areas include, but are not limited to, disease mechanism studies, stem cell biology, genomic data, biomarkers, aggregated clinical/environmental data and/or patient-reported data to develop personalized medical care, decision support tools, new methods of working with precision medicine data and its integration with electronic health records, and new individualized approaches to effectively educate and communicate with patients.

These pilot grants are intended to support feasibility studies at Columbia that will establish a basis for applying for further research funding. As such, pilot grants are intended to generate preliminary data required to produce competitive grant applications to outside funders. Up to five studies in total will be funded.

Goals of the Program:

  • The Vagelos Precision Medicine Pilot Grant program is made possible by the generous gift of Roy and Diana Vagelos to the Columbia Precision Medicine Initiative (CPMI) and is intended to support ground-breaking basic research in the field of precision medicine.
  • Precision Medicine Resource of the Irving Institute for Clinical and Translational Research (IICTR) seeks to facilitate research studies to improve diagnosis and treatment of disease, and ultimately improve maintenance of health through more accurate prediction of disease risk.
  • The Herbert Irving Comprehensive Cancer Center (HICCC) is dedicated to understanding the biology of cancer and to applying that knowledge to the design of cancer therapies and prevention strategies.

Eligibility:

  • Applicants must have a full-time Columbia University/Columbia University Irving Medical Center faculty appointment at the rank of an Assistant, Associate, or Full Professor.
  • NY State Psychiatric Institute faculty members who do not have a full-time faculty appointment at CU/CUIMC are eligible to apply as co-PIs; they can also be listed as co-investigators or consultants.
  • Preference will be given to applications from early- and mid-career investigators.
  • Applications with an interdisciplinary and collaborative approach involving several departments or schools will be viewed favorably.
  • Collaborations between Morningside, Manhattanville, and Irving Medical Center campuses are encouraged.
  • Each team is limited to six (6) members.
  • Underrepresented groups are strongly encouraged to apply.
  • Applicants are eligible to submit only one application as PIs or co-PIs per award cycle, but they could be listed as co-investigators/consultants on multiple applications.
  • Faculty who have received Precision Medicine pilot award funding from CPMI, HICCC, and the Irving Institute as PIs and/or co-PIs within the last 3 years are not eligible to apply as PIs and/or co-PIs in this cycle, but they could be listed as co-investigators/consultants on applications.
  • External investigators (non-Columbia/non-NYSPI affiliates) could be listed on applications as consultants (paid or unpaid; if paid, compensation details should be included in the budget).

Budget: $100,000 per fiscal year.

Funding: Each Precision Medicine Pilot Grant program award will provide funding for a one-year pilot grant of up $100,000 to cover direct costs based on the project’s needs. Funding should be directed to specific experimental activities that will establish the basis for applying for further research funding from outside entities, i.e. government, foundations, and industry. We encourage that the majority of funds be utilized for project-specific study experiments, a smaller portion of the funds may be used towards post-doctorate researcher, graduate student, and technician salaries. Funding may not be used towards PI/co-PI or co-investigator salaries.

Duration: 1 year.
 
Submit documents by Friday, December 3rd, 2021, via this link:
https://columbiaprecisionmed.smapply.io

Proposals are requested for one-year pilot studies in precision medicine. Studies must be relevant to advancing precision medicine basic sciencepre-clinical/clinical approaches to tailoring medical care (prevention, diagnosis, and/or treatment) to the individual patient, and/or precision cancer research.

Example areas include, but are not limited to, disease mechanism studies, stem cell biology, genomic data, biomarkers, aggregated clinical/environmental data and/or patient-reported data to develop personalized medical care, decision support tools, new methods of working with precision medicine data and its integration with electronic health records, and new individualized approaches to effectively educate and communicate with patients.

These pilot grants are intended to support feasibility studies that will establish a basis for applying for further research funding. As such, pilot grants are intended to generate preliminary data required to produce competitive grant applications to outside funders. 

Up to five studies in total will be funded.

The Vagelos Precision Medicine Pilot Grant program is made possible by the generous gift of Roy and Diana Vagelos to the Columbia Precision Medicine Initiative (CPMI) and is intended to support ground-breaking basic research in the field of precision medicine. Precision Medicine Resource of the Irving Institute for Clinical and Translational Research (IICTR) seeks to facilitate research studies to improve diagnosis and treatment of disease, and ultimately improve maintenance of health through more accurate prediction of disease risk. The Herbert Irving Comprehensive Cancer Center (HICCC) is dedicated to understanding the biology of cancer and to applying that knowledge to the design of cancer therapies and prevention strategies.

Eligibility: Applicants must have a full-time Columbia University faculty appointment at the rank of an Assistant, Associate, or Full Professor. Preference will be given to proposals from early and mid-career investigators. Studies may involve more than one department, including collaboration between Morningside, Manhattanville, and Irving Medical Center campuses. Applications with an interdisciplinary and collaborative approach with other departments or schools will be viewed favorably. Each team is limited to six (6) members. Underrepresented groups are strongly encouraged to apply. Faculty who have received Precision Medicine pilot award funding from CPMI, HICCC, and Irving Institute as PIs and/or co-PIs within the last 3 years are not eligible to apply.

Budget$100,000 per fiscal year.

Funding: Each Precision Medicine Pilot Grant program will provide funding for a one-year pilot grant of up $100,000 based on the project’s needs. Funding should be directed to specific experimental activities that will establish the basis for applying for further research funding from outside entities, i.e. government, foundations, and industry. We encourage that the majority of funds be utilized for project-specific study experiments, a smaller portion of the funds may be used towards post-doctorate researcher, graduate student, and technician salary. Funding may not be used towards PI salary.

Duration: 1 year

Deadline: 11:59pm on Tuesday, December 1, 2020

Application can be found here: 
https://columbiaprecisionmed.smapply.io

The Vagelos Precision Medicine supplemental funding for mouse models is made possible by the generous gift of Roy and Diana Vagelos, to the Columbia Precision Medicine Initiative, and it is intended to support ground-breaking research in the field of precision medicine.

Proposals are requested to generate new mouse models of disease based on likely causal variants discovered by human sequencing, primarily in constitutional genetics, not alterations in neoplasms. The program will only subsidize new projects, and not retroactively fund or supplement projects that have already begun. Funds will be awarded to subsidize costs of mouse mutant strain design and construction from approved service providers. The subsidy will provide 2/3 of the total quoted cost per model, with the balance provided by the PI.

A maximum of two models per request per investigator will be permitted.  Funding for approximately 8-10 new models is anticipated in this review cycle.

Eligibility: Applicants must have a full-time Columbia University faculty appointment (including NYPSI and clinical faculty) at the rank of an Assistant, Associate, or Full Professor.

Application Directions: Prepare description (2-page maximum) for each model as follows. (Those applying for 2 models in separate genes should submit a separate application for each).

  • Investigator name, home department, contact information
  • Project title
  • Description of human mutation and mouse orthologue to be targeted
  • How the mutation was selected and the basis for disease involvement
  • Relevance to investigator research interests and to precision medicine
  • Describe the way the mice will be studied
  • Any other information that would shed light on the likelihood of success

Provide the following supporting information:

  • Provide the cost, the approach to model design and development, including milestones and timelines from a service provider of the applicant’s choosing. Formal quotes are encouraged but not required upon proposal submission.  However, funds will not be released until a formal quote is provided.
  • Work with Institute for Comparative Medicine to ensure approval of purchase orders and eventual delivery of mice into a CU vivarium (Business manager: Seth Mayersohn sm3580; Veterinary services - Andrea Hubbard ah2911)
  • Review checklist points 1 through 7 (next page)

Submit each application by January 27, 2020, via the Columbia Precision Medicine Initiative grants management websitehttps://columbiaprecisionmed.smapply.io/.

Applications will be examined by a review committee, headed by Program Directors: Wayne Frankel, PhD and Ali Gharavi, MD, with notification of funding in April, 2020. Any questions may be sent to [email protected]

Checklist

1. Does a mouse carrying the mutation, or one very similar to it, already exist?  What is known about viability, transmission and availability?  Example websites to check:

2. Consider the type of mutation desired (N.b.: more complex models may cost more)

  • Simple null allele (knockout)
    • Conditional knockout (e.g. lox-p sites flanking exon)
  • Simple knockin (point mutations)
    • Complex knockin (e.g. humanization of whole exons or genes)
    • Conditional knockin (e.g. flox-stop cassette or inverted exon)

3. Mouse strain background (e.g. C57BL/6J, 129/SvImJ, FVB/NJ): Are you targeting in direct zygotes or in ES cells? Some commercial vendors may not be licensed to target certain mouse strains or sub-strains from other vendors.  Check with your service provider.

4. Will you need “all in” service (from project design to receipt of proven carriers), or do you plan to participate in the screening for, and development of, the mutant line? Some vendors will only offer all-in service, which may be more expensive but may provide conveniences such as proven germline transmission, robust validation of the desired sequence without undesired contaminating mutations, and fecundity and viability of mice carrying the mutation. Some may offer a la carte service that saves out of pocket-cost, but not screening and initial breeding.

5. Do you already have an IACUC protocol? Ensure the expected mice are on your protocol and funding is in place for animal housing, in synchrony with the estimated delivery date

6. We strongly recommend that you have funds to cryopreserve the strain, or have that included as an integral part of the quotation (if offered by the same service provider). CPMI will not pay for separate cryopreservation or for storage costs).

7. PI must make sure the service provider is likely to be approved by ICM as a source - this program will not pay for quarantine or re-derivation services. Also note that Columbia Purchasing may require either sole source justification or competing quotes. Examples of commercial or local academic service providers that may offer mouse gene targeting include:

  • Columbia HICCC Transgenic Core
  • The Jackson Laboratory
  • Charles River Laboratories
  • Bioincyte
  • Cyagen
  • genOway
  • Ingenious
  • Leveragen
  • Miramus
  • MSKCC Mouse Genetics Core

Proposals are requested for one-year pilot studies in precision medicine. Studies must be relevant to advancing precision medicine basic science, pre-clinical/clinical approaches to tailoring medical care (prevention, diagnosis, and/or treatment) to the individual patient, and/or precision cancer research.

Example areas include, but are not limited to, disease mechanism studies, stem cell biology, genomic data, biomarkers, aggregated clinical/environmental data and/or patient-reported data to develop personalized medical care, decision support tools, new methods of working with precision medicine data and its integration with electronic health records, and new individualized approaches to effectively educate and communicate with patients.

These pilot grants are intended to support feasibility studies that will establish a basis for applying for further research funding. As such, pilot grants are intended to generate preliminary data required to produce competitive grant applications to outside funders.  

Up to five studies in total will be funded.

The Vagelos Precision Medicine Pilot Grant program is made possible by the generous gift of Roy and Diana Vagelos to the Columbia Precision Medicine Initiative (CPMI) and is intended to support ground-breaking basic research in the field of precision medicine. Precision Medicine Resource of the Irving Institute for Clinical and Translational Research (IICTR) seeks to facilitate research studies to improve diagnosis and treatment of disease, and ultimately improve maintenance of health through more accurate prediction of disease risk. The Herbert Irving Comprehensive Cancer Center (HICCC) is dedicated to understanding the biology of cancer and to applying that knowledge to the design of cancer therapies and prevention strategies.

Application deadline: 11:59 PM ET on Friday, November 29th, 2019

Precision Medicine & Society Pilot Grant Program

Center for Research on Ethical, Legal and Social Implications (ELSI) of Psychiatric, Neurologic & Behavioral Genetics; Columbia University Irving Medical Center

Precision Medicine & Society Program; Columbia University

Pilot grant awards for Columbia faculty and postdocs are available, up to a maximum of $20,000, from the Center for Research on Ethical, Legal and Social Implications (ELSI) of Psychiatric, Neurologic & Behavioral Genetics, Department of Psychiatry, Columbia University Irving Medical Center and the Precision Medicine & Society (PM&S) Program, Columbia University. The awards are designed to support pilot work on ethical, social, economic, legal, historical or philosophical issues related to genetics and precision medicine. Proposals addressing issues relating to psychiatric, neurologic or behavioral genetics are especially encouraged; however, proposals relating to other areas of precision medicine are also welcome. Examples of possible projects include implications of new genomic technologies for prenatal and neonatal screening; privacy issues  in genetics; genetic diagnosis and identity; social and psychological impacts of geneticization; legal and policy implications of precision medicine or behavioral genetics; the use of algorithms and health-tracking apps; and the impact of precision medicine on the health insurance industry.

Projects should have the potential to lead to additional federal or foundation funding. Involvement of faculty from more than one discipline is encouraged. Non-Columbia faculty may participate in a project so long as a Columbia faculty member or postdoc is the principal investigator; graduate students may participate so long as a Columbia faculty member is the PI. Applicants should submit:

  • A 3-page research proposal that details the specific aims and background of the study, preliminary data (if any), research plan (including plan for data analysis), innovation/significance, and future plans.
  • A NIH-style biosketch or curriculum vitae for the PI and any co- investigators.
  • A detailed budget with justification. Funds may be used to support salaries and other research costs.

Proposals will be scored on the basis of:

  • Innovativeness and significance of the research.
  • Quality and intellectual merit of the project.
  • Likelihood of serving as the foundation for obtaining further funding and plan for seeking this funding.

Studies “piggy-backed” on existing research projects are welcome. Priority will be given to junior faculty who are interested in research in this area. Both the Center and the PM&S Program actively support diversity and welcome submissions from investigators that address diverse populations, and proposals from investigators of all backgrounds, especially those underrepresented in ELSI research.

Proposals should be submitted electronically as a single PDF document to Paul Appelbaum at [email protected] by November 15, 2019. Funding will begin November 29, 2019 and funds must be utilized by June 30, 2020. A final project report will be required. Direct questions to Paul S. Appelbaum, MD, Director, Center for Research on Ethical, Legal and Social Implications (ELSI) of Psychiatric, Neurologic & Behavioral Genetics, at [email protected] or Gil Eyal, PhD, Co-Chair, Precision Medicine & Society Program, at [email protected]

Additional information about the Center is available at braingenethics.cumc.columbia.edu, and about the PM&S Program at https://precisionmedicine.columbia.edu/content/precision-medicine-and-society

The Vagelos Precision Medicine supplemental funding for mouse models is made possible by the generous gift of Roy and Diana Vagelos, to the Columbia Precision Medicine Initiative, and it is intended to support ground-breaking research in the field of precision medicine.

Proposals are requested to generate new mouse models of disease based on likely causal variants discovered by human sequencing, primarily in constitutional genetics, not alterations in neoplasms. The program will only subsidize new projects, and not retroactively fund or supplement projects that have already begun. Funds will be awarded to subsidize costs of mouse mutant strain design and construction from approved service providers. The subsidy will provide 2/3 of the total quoted cost per model, with the balance provided by the PI.

A maximum of two models per request per investigator will be permitted.  Funding for approximately 8-10 new models is anticipated in this review cycle.

Eligibility: Applicants must have a full-time Columbia University faculty appointment (including NYPSI and clinical faculty) at the rank of an Assistant, Associate, or Full Professor.

Application Directions: Prepare description (2-page maximum) for each model as follows. (Those applying for 2 models in separate genes should submit a separate application for each).

  • Investigator name, home department, contact information
  • Project title
  • Description of human mutation and mouse orthologue to be targeted
  • How the mutation was selected and the basis for disease involvement
  • Relevance to investigator research interests and to precision medicine
  • Describe the way the mice will be studied
  • Any other information that would shed light on the likelihood of success

Provide the following supporting information:

  • Provide the cost, the approach to model design and development, including milestones and timelines from a service provider of the applicant’s choosing. Formal quotes are encouraged but not required upon proposal submission.  However, funds will not be released until a formal quote is provided.
  • Work with Institute for Comparative Medicine to ensure approval of purchase orders and eventual delivery of mice into a CU vivarium (Business manager: Seth Mayersohn sm3580; Veterinary services - Andrea Hubbard ah2911)
  • Review checklist points 1 through 7 (next page)

Submit each application by January 30th, 2019, via the Columbia Precision Medicine Initiative grants management website: https://columbiaprecisionmed.smapply.io/.

Applications will be examined by a review committee, headed by Program Directors: Wayne Frankel, PhD and Ali Gharavi, MD, with notification of funding in April, 2019. Any questions may be sent to [email protected]

Checklist

1. Does a mouse carrying the mutation, or one very similar to it, already exist?  What is known about viability, transmission and availability?  Example websites to check:

2. Consider the type of mutation desired (N.b.: more complex models may cost more)

  • Simple null allele (knockout)
    • Conditional knockout (e.g. lox-p sites flanking exon)
  • Simple knockin (point mutations)
    • Complex knockin (e.g. humanization of whole exons or genes)
    • Conditional knockin (e.g. flox-stop cassette or inverted exon)

3. Mouse strain background (e.g. C57BL/6J, 129/SvImJ, FVB/NJ): Are you targeting in direct zygotes or in ES cells? Some commercial vendors may not be licensed to target certain mouse strains or sub-strains from other vendors.  Check with your service provider.

4. Will you need “all in” service (from project design to receipt of proven carriers), or do you plan to participate in the screening for, and development of, the mutant line? Some vendors will only offer all-in service, which may be more expensive but may provide conveniences such as proven germline transmission, robust validation of the desired sequence without undesired contaminating mutations, and fecundity and viability of mice carrying the mutation. Some may offer a la carte service that saves out of pocket-cost, but not screening and initial breeding.

5. Do you already have an IACUC protocol? Ensure the expected mice are on your protocol and funding is in place for animal housing, in synchrony with the estimated delivery date

6. We strongly recommend that you have funds to cryopreserve the strain, or have that included as an integral part of the quotation (if offered by the same service provider). CPMI will not pay for separate cryopreservation or for storage costs).

7. PI must make sure the service provider is likely to be approved by ICM as a source - this program will not pay for quarantine or re-derivation services. Also note that Columbia Purchasing may require either sole source justification or competing quotes. Examples of commercial or local academic service providers that may offer mouse gene targeting include:

  • Columbia HICCC Transgenic Core
  • The Jackson Laboratory
  • Charles River Laboratories
  • Bioincyte
  • Cyagen
  • genOway
  • Ingenious
  • Leveragen
  • Miramus
  • MSKCC Mouse Genetics Core

We are pleased to announce the winners of the 2nd Roy and Diana Vagelos Precision Medicine Pilot Awards. We were impressed with the response and with the broad range of proposals from Columbia faculty. The standard of the 34 applications we received was very high, and investigators came from all Columbia campuses. Thanks to all who submitted proposals and to those who participated in the review process.
 
The Roy and Diana Vagelos Awards are a cornerstone of the CPMI mission: to establish world class academic research centers of excellence to build precision medicine as a basic and applied science at Columbia. Seeding basic research in precision medicine with these awards is an efficient way of converting this money to external research grants and we look forward to this return on investment in due course.
 
The three winning proposals reflect the high standard and the broad base of precision medicine basic science research being conducted and conceived at Columbia. They cover epilepsy research; neuro oncology research; and developing a synthetic cell communication tool for tissue engineering.
 
The winning proposals are:
1. Development of novel therapies for STXBP1 encephalopathy.
Michael Boland Ph.D. Dept of Neurology, Institute for Genomic Medicine; Wayne Frankel Ph.D. Dept of Genetics & Development; Sophie ColomboSabrina Petri, IGM
 
Mutations in STXBP1 result in a disorder characterized by infantile epilepsy, severe cognitive impairment, and slow progression in GI and motor development. Medications may control seizures, but have no effect on other aspects of development. In children with only one functioning copy of the gene, there is no correlation between severity of seizures and cognitive impairment suggesting that separate mechanisms are involved.  We will study human neuronal and mouse models of STXBP1 haploinsufficiency at the organism, neuronal network, and cellular level in order to identify the most robust features for testing therapies. Screening will be performed on human neuronal networks, and brain region-specific mouse neuronal networks in an effort to identify neuroactive, FDA-approved compounds that correct defects.  We will also develop and test two different gene therapy approaches for correcting associated developmental phenotypes.
 
2. Molecular characterization of gliomas under immunotherapy.
Raul Rabadan PhD, Dept of Bioinformatics; Systems Biology; Fabio Iwamoto MD, Dept of Neurology (Neuro-oncology division); Junfei Zhao, PhD.
 
Glioblastoma is the most common and most aggressive primary brain tumor in adults, with extremely poor prognosis.  While these patients have infrequent tumor responses to immunotherapies compared to melanoma and non-small cell lung cancers, 10% of patients showed limited positive responses. We are extending our current efforts in the molecular characterization of these patients  by extensive profiling the genome of the tumor and the surrounding immune cells of a cohort of IDH1 mutant gliomas treated with immunotherapies after standard treatment. These tumors have been reported to have very high rates of mutations (hypermutation), a genomic characteristic that have been associated to response to immunotherapies. Our work  will identify novel molecular markers of response to immunotherapies by studying specific cohort of these patients treated at Columbia University. 
 
3. Exploiting the basic mechanism of Notch activation to develop new diagnostic, therapeutic and tissue engineering tools for precision medicine.
Gary Struhl PhD; Paul Langridge PhD. Dept of Genetics and Development (in Neuroscience); Zuckerman Mind Brain Behavior Institute
 
Synthetic biology involves engineering cells so that they perform useful tasks. An ambitious aim of the field is to customize the behavior of cells so that they form tissues for the repair of wounds, correction of birth defects, regeneration of damaged limbs or creation of organ substitutes. Central to this goal is enabling cells to communicate using tailor-made components. Our research describes the development of a tool for devising and testing this synthetic cell-communication technology. We will establish a system with entirely synthetic cell-communication that functions alongside natural biological processes and determine how these tools can be used to organize cell behavior and alter the morphology of a tissue. In the future such bespoke systems may well be further customized through their application in precision medicine and lead to therapeutic and biotechnological advances that will help fight disease and repair defects. 

The Precision Medicine Junior Faculty and Post-Doctoral travel for child care subsidy program is funded through the Columbia Precision Medicine Initiative. This program assists scholars to attend conferences in the field of Precision Medicine by subsidizing travel costs associated with child care. Examples of child care costs include: Care giver to accompany you and your child; On-site childcare at the conference; Purchase of a ticket for e.g. a grandparent to come to your home, or to the conference, for childcare. The cost of regular day care or pre school at home is not a qualifying expense.

One of Columbia University’s core values is to expand scholarship, while increasing inclusion and success of highly qualified candidates. This program aims to expose future leaders in precision medicine to current leaders in the field. Scholars will increase their visibility and gain access to senior worldwide faculty in precision medicine.

Eligibility: Columbia Junior Faculty; Columbia post-doc with 2 years’ experience.

Budget: up to $600 per award

Application:

  • Personal Statement (250 words): Why is your chosen conference important in your field? How would you benefit from this scholarship?
  • Explanation for budget required

Submit your application here.

Deadline: Rolling

Factors for evaluation:

  • Relevance of conference to PM intellectual themes
  • Personal statement
  • Publication record
  • Possibility of a speaking role at the conference

 

If there are more qualified applications than awards available, applications will be entered into a lottery.

Questions? Email [email protected]

The Vagelos Precision Medicine supplemental funding for mouse models is made possible by the generous gift of Roy and Diana Vagelos, to the Columbia Precision Medicine Initiative, and it is intended to support ground-breaking research in the field of precision medicine.

Proposals are requested to generate new mouse models of disease, discovered by human sequencing, primarily in constitutional genetics, not alterations in neoplasms. This program will only subsidize new projects, and not retroactively fund or supplement projects that have already begun. Funds will be awarded to subsidize costs of mouse mutant strain design and construction (e.g. by CRISPR) from approved service providers. The subsidy will be up to 66% of the total quoted cost per mutant strain, or up to $15,000 per mutant strain, whichever is less.

The development of approximately 20 models will be supported in the first year. A maximum of two models per request per investigator will be permitted.

Eligibility: Applicants must have a full-time Columbia University faculty appointment (including NYPSI and clinical faculty) at the rank of an Assistant, Associate, or Full Professor.

Application Directions: Prepare description (2-page maximum) for each model as follows:

  • Investigator name, home department, contact information
  • Project title
  • Description of human mutation and mouse orthologue to be targeted
  • How the mutation was selected and the basis for disease involvement
  • Relevance to investigator research interests and to precision medicine
  • Describe the way the mice will be studied
  • Any other information that would shed light on the likelihood of success

Provide the following supporting information:

  • Obtain design, prices, model development updates and timelines from service providers (quotes not required for application, but funds will not be released until quote is received)
  • Work with Institute for Comparative Medicine to ensure approval of purchase orders and eventual delivery of mice into a CU vivarium (Business manager: Seth Mayersohn sm3580; Veterinary services - Andrea Hubbard ah2911)
  • Review checklist points 1 through 7 below

Applications will be examined by the review committee, headed by Program Directors: Wayne Frankel, PhD and Ali Gharavi, MD, on a rolling basis with notification of funding within a month of review.

Submit application by March 30th 2018, as one single pdf, to the Program Administrator at [email protected]

Checklist

1. Does the mouse carrying the mutation already exist? What is known about its viability, transmission and availability? Example websites to check:

  • www.informatics.jax.org
  • www.komp.org
  • www.mousephenotype.org/data/search

2. Type of mutation desired (more complex models will cost more)

  • Simple null allele (knockout)
  • Conditional knockout (lox p sites flanking exon)
  • Simple knockin (point mutation(s) only)
  • Complex knockin
  • Site-specific reporter or cre gene insertion
  • Conditional point mutation (e.g. flox-stop cassette)

3. Mouse strain background (e.g. C57BL/6J, 129/SvImJ, FVB/NJ): Are you targeting in direct zygotes or in ES cells? Some vendors may not be licensed to legally target certain mouse strains or sub-strains from other vendors. Check with your service provider on strains they use.

4. “All in” service (from initial design to receipt of proven carriers), or participate in the screening for, and development of, the mutation? Some vendors will only offer all-in service, which may be more expensive but gives the convenience of proven germline transmission and fecundity and viability of mice carrying the mutation; Others may offer a la carte services that will save out of pocket-costs but do not do the screening and initial breeding.

5. Do you already have a IACUC protocol for studying mice? Ensure the expected mice are on your protocol and funding is in place for animal housing, in synchrony with the estimated delivery date

6. We strongly recommend that you have funds to cryopreserve the strain, or have that included as an integral part of the quotation (if it is offered by the same service provider). CPMI will not pay for separate cryopreservation or for storage costs).

7. PI must have their service provider approved by ICM as a mouse vendor - this program will not pay for quarantine or re-derivation services. Please note Columbia purchasing may require sole source justification. Examples of service providers that offer mouse gene targeting (may not be approved by CU and the ICM)

  • Bioincyte
  • HICCC Transgenic Core (Columbia – in ICRC)
  • Cyagen
  • Ingenious
  • The Jackson Laboratory
  • Leveragen
  • MSKCC Mouse Genetics Core

We are pleased to announce the winners of the inaugural Roy and Diana Vagelos Precision Medicine Pilot Awards. We were impressed with the response and with the broad range of proposals from Columbia faculty. The standard of the 56 applications we received was very high, and investigators came from all Columbia campuses. Thanks to all who submitted proposals and to those who participated in the review process.
 
The three winning proposals reflect the high standard, the broad base, and the collaborative nature of precision medicine basic science research being conducted and conceived at Columbia:
Two proposals are a collaboration between junior and senior faculty;
Two feature collaboration between investigators on different campuses;
One, a collaboration between basic and clinical researchers.
 
The winning proposals are:
Programmable probiotics for personalized cancer immunotherapy.
Nicholas Arpaia, PhD, Assistant Professor, Dept. of Microbiology & Immunology; Tal Danino, PhD, Assistant Professor, Dept. of Biomedical Engineering

Objectives:
First, engineer probiotic strains that locally release immunotherapeutics along with tumor-specific antigenic peptides within the tumor microenvironment. Investigators will use synthetic biology approaches to engineer genetic circuits using a strain of E. Coli, which will permit selective growth and synchronized lysis within the hypoxic core of a solid tumor, thus allowing for localized release of plasmid-encoded immunotherapeutics and tumor-specific antigens.
 
Second, characterize anti-tumor immune responses following delivery of engineered immunotherapeutic bacteria encoding tumor-specific antigenic peptides, or reported neoantigens. Investigators will quantify antigen specific anti-tumor T cell responses in an animal model and characterize cytokine production, and hypothesize that bacterial co-delivery will enhance anti-tumor immunity.
 
Third, assess the durability and systemic efficacy of anti-tumor responses elicited by engineered bacterial strains. Investigators hypothesize that the locally primed anti-tumor immunity will lead to durable antigen specific immune responses with long lasting eradication of systemic metastases.
 
Future work:
This proposal leverages expertise in synthetic biology and immunology to engineer probiotic strains of bacteria that selectively colonize tumors and elicit systemic, neoantigen-guided anti-tumor immunity. In future studies, investigators will develop methodologies for identifying patient-specific tumor neoantigen repertoires to create personalized bacterial strains for patient- and tumor-specific immunotherapy.



Elucidating the tissue-specific molecular mechanisms underlying disease associations through integrative analysis of genetic variation and molecular network data.
Tuuli Lappalainen, PhD, Assistant Professor, Dept. of Systems Biology; Junior investigator and Core Member, New York Genome Center; Harmen J Bussemaker, PhD, Professor, Dept. of Biological sciences; Dept. of Systems Biology

Objectives:
The first goal is to dissect the molecular mechanisms underlying tissue-specificity of genetic regulatory variants. Using extensive data produced by the Genome Tissue Expression (GTEx) project, which catalogued thousands of genetic associations with gene expression across hundreds of individuals and dozens of human tissues, the investigators will analyze how the cellular environment modifies the effect size of genetic cis-regulatory variants in the human genome. They will also investigate to what extent these regulatory effects can be rationalized in terms of allelic variation in the binding affinity of transcription factors as predicted from the DNA sequence.
 
The second goal is to map network-level regulatory variants that cause protein-level transcription factor activity to vary between individuals. The investigators will infer TF activity based on DNA binding specificity models of human TFs, and use it as a tissue-specific parameter of the cellular environment. They will also map trans-acting genetic variants that affect TF activity (coined ‘aQTLs’ by one of the investigators) in each tissue. It is anticipated that the trans-acting loci identified by this analysis will be of major interest to basic biology researchers, and will also help explain GWAS associations to complex disease.
 
Future work:
This proposal hopes to elucidate which transcription factors are driving the functional impact and tissue specificity of any particular eQTL. Identifying the transcription factors that are upstream regulators of genetic regulatory variants provides a starting point for mapping the environmental stimuli or drugs that modify these transcription factors. Interactions with disease associations can be studied and validated in available large-scale ‘phenome’ data sets. Furthermore, any aQTLs that colocalize with GWAS loci provide important starting points for further mechanistic study.


 
Notch2 polymorphisms as predictors of low β-cell mass and increased type 2-diabetes risk.
Utpal Pajvani, MD, PhD, Herbert Irving Assistant Professor of Medicine, Dept. of Medicine, Endocrinology; Dieter Egli, PhD, Maimonides Assistant Professor of Developmental Cell Biology, Dept. of Pediatrics; Domenico Accili, MD, Russell Berrie Foundation Professor of Diabetes, Dept. of Medicine; Chief of Endocrinology Division; Director of the Columbia University Diabetes and Endocrinology Research Center.

Objectives:
First, use CRISPR to generate null NOTCH2 alleles, on the background of a reporter IPS line encoding GFP in the insulin locus to allow tracking of the cells in vitro and in vivo. After differentiation to β-cells in vitro and in vivo, test the repercussions of loss of NOTCH2 on β-cell biology.
Second, determine the mechanism of reduced NOTCH2 expression and other possible molecular repercussions of the rs10923931 SNP, and determine effects on β-cell Notch activity and downstream effects on β-cell proliferation and maturation.
 
Future Work:
Investigators predict that NOTCH2 T2D risk variants decrease proliferation of pancreatic progenitors and/or fully developed cells due to reduced β-cell NOTCH2 expression, which in turn reduces β-cell Notch activity. Future work will focus on translational studies, to cross-reference individual genomic information to β-cell mass data from PET imaging. In addition, investigators will test whether the NOTCH2 variant is associated with lower insulin/C-peptide in T2D patients, and whether the NOTCH2 variant will predict early need for insulin therapy in susceptible patients.

Irving Institute for Clinical and Translational Research

The Precision Medicine Research Fellowship aims to create the next generation of leaders in the development and application of Precision Medicine science and methods to improve public health. This new research fellowship in precision medicine will train physicians/researchers as Postdoctoral Research Scientists to use genomics and complex clinical data to improve clinical care and clinical outcomes by tailoring prevention, screening, and medical interventions based upon individual patient characteristics.
 
Qualifications:
Applicants must have a PhD, MD, DDS, or comparable doctoral degree from an accredited domestic or foreign institution.
 
Duration:  2 years
Award Amount:  $200,000 ($100,000 per year)
Quantity:  Up to 2 per year
 
Application Deadline:  5:00pm EDT, Friday, May 18, 2018
Start Date:  July 1, 2018
 
Visit here for more information and to download an application.
 
Accelerating Discoveries Toward Better Health
irvinginstitute.columbia.edu