Research
For the last thirty-five years, my research focus has always been to identify the presence of cancer as early as possible and to prevent it from developing into its end-stage monstrosity.
I started my career by studying and treating acute myeloid leukemia (AML). Very soon, it was obvious to me that the pathology and continuously evolving nature of the disease makes it impossible to find a cure for it in my lifetime. Instead, I turned my attention to studying the pre-leukemic disorders grouped under the name, Myelodysplastic Syndromes (MDS) because a third of the patients evolve to AML. The ides was simple; diagnose at pre-leukemic stage and prevent it from developing into leukemia.
With the above goal in mind, I started to bank samples of blood and marrows on my MDS and AML patients starting in 1984. This has results in the Tissue Repository housed at Columbia University with >60,000 samples collected over 35 years.
Collaborating with a leading group from Dana Farber Cancer Center, we published a study in the New England Journal of Medicine in 2011 showing the prognostic and clinical significance of mutations in five genes by comparing >400 MDS patients and 200 normal controls from the Tissue Repository. This observation changed the disease paradigm since many treatment decisions depended on the presence or absence of the mutations. Several companies rapidly offered the five-gene signature as a prognostic test paid for by Medicare and all insurers because of its clinical importance.
Since then, we have regularly published small, focused studies on small numbers of Tissue Repository samples interrogating various aspects of genomics and transcriptomics in high profile journals.
The focus of my research now is to study serial samples from thousands of patients banked in the Tissue Repository in depth. The goals are straightforward:
- To identify the earliest footprints of pre-leukemia and leukemia
- To pinpoint the risk factors: exome (genes) and exposome (what one is exposed to) that make one susceptible to cancer
- To start monitoring cancer survivors who are at high risk for the appearance of The First Cell
- Ultimately, to develop implantable devices that monitor and detect the first cells through constant surveillance of healthy individuals from birth to death
So why don’t I have a better answer for my patients yet?
First, the samples had to be collected on enough patients whose disease made the journey from MDS to AML. Second, the technology had to be developed.
And now, the resources are needed to perform a thorough examination of serial samples using pan-omics (Genomics, transcriptomics, proteomics, metabolomics) and relate the results to the clinical and other pathologic manifestations of the disease, its natural history, the factors that determine response to therapy.
With these goals in mind, and armed with the samples and the technology, The First Cell Center at Columbia University has been envisioned. Our aim is to raise the funds needed for the detailed study of the Tissue Repository as described above.
THE FIRST CELL CENTER (FCC)
Why should the public support FCC rather than the hundreds of other organizations dedicated to cancer research?
FCC is unique because of the Tissue Repository and the active patients who are coming to clinic by the hundreds every month.
I do not want to establish an institute that hires 100 researchers and then spend the rest of my life trying to raise funds to support their research projects.
Rather, the funds raised will go directly to pay for the tests needed and the analysis of the resulting terabytes of data generated in order to find the footprints of the first cells.
We propose to collaborate with top-notch researchers around the country with complimentary expertise.
FIVE YEAR RESEARCH PLAN
- Year 1-3
- Identify proteomics, metabolomics and germline markers
- Build data clouds for each patient through serial samples
- Year 1-4
- Microfluidic devices for early detection of biomarkers
- Year 2-4
- Transcriptomics
- Peptide development
- Collection and storage of peripheral blood (cells/serum) and buccal cells on aged normal individuals so that we have our own aged-matched well characterized sample set for validations by year 5
- Year 3-4
- Microbiome study
- Imaging with tumor specific peptides
- Year 3-5
- Assimilation of Pan-Omics
- Identify best analytes and genomic signatures
- Year 5
- Start screening normal individuals and other cancers