Our Research Focus

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We focus primarily on identifying and characterizing therapy-relevant dual-impact phosphotyrosine-altering germline variants, termed “pTyr-SNVs.” These variants play pleiotropic roles in both tumor-intrinsic and tumor-extrinsic signaling pathways. Due to the limited basic biological knowledge available for pTyr-SNVs, they are classified as variants of uncertain significance (VUS), or Class 3, according to ACMG guidelines in ClinVar, and are currently not considered in clinical decision-making.

We have shown that pTyr-SNV variants, such as rs31855 G>A; FGFR4 p.Gly388Arg, exhibit non-canonical proximal phosphotyrosine signaling functions (Ulaganathan et al., Nature, 2015; Ulaganathan VK & Ullrich A, MCO, 2016) and thereby exert pleiotropic effects, not only by accelerating cancer progression but also by modulating the effectiveness of anti-tumor immune responses within the tumor microenvironment (Kogan et al., Journal of Clinical Investigation, 2018). Over the past several years, we have functionally characterized a few pTyr-SNVs, including MST1R, FLT3, and ITGA4, and are continuously expanding our portfolio of biologically validated pTyr-SNVs.

At the IMGAG, directed by Prof. Dr. med. Olaf Riess and co-directed by PD Dr. med. Tobias Haack, we have identified several disease-associated pTyr-SNVs (unpublished data). Some of these variants may play pleiotropic roles in the interplay between complex human diseases, including autoimmunity, cancer, and neurodegeneration. To translate this knowledge into clinical impact, more detailed molecular and functional knowledge concerning pTyr-SNVs needs to be generated in order to decipher the mechanistic basis of these genetic associations.

To this end, we are developing both genetic and non-genetic methodologies to accelerate the molecular and functional characterization of patient-associated, therapy-relevant pTyr-SNV VUS, utilizing both hematopoietic and non-hematopoietic cellular model systems.

Tool / Method Name	Type	Utility	Reference
TraPS-VarI	Variant Analysis Tool	Identifies ITIM, ITAM and SRTM-altering SNVs	Ulaganathan VK, Sci Reports 2020
MAGIC Knockdown	Pathogenic protein variant neutralization method	Precise silencing of protein sequence variants in cells	Ulaganathan VK, ChemBioChem, 2022
A reporter for Cancer Metastasis	Assay for early detection of cancer metastasis	Method awaits clinical validation	Unpublished
Syngeneic Cocultivation:TCR-transgenic T cells & Cancer cells	Assay for characterization of immunologically-relevant pTyr-SNVs	Assay to measure TCR signaling alteration triggered by tumor antigen presentation	Ulaganathan et al., Journal of Genetics & Genomics, 2023

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Webinars and Podcasts

We are committed to pursuing original ideas.

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Webinar Hosted by The-Scientist Magazine

For more information visit: The Scientist’s Journal Club: Cancer

A Novel Cell Surface Marker for Anastasis

Podcasters explore how the discovery happened and its implications.

Assay to Uncover Immunotherapy-relevant pTyr-SNVs

Podcasters discuss the syngeneic co-cultivation method to study pTyr-SNVs

MAGIC Knockdown: A Paradigm-shifting Approach to Target Pathogenic Genetic Variants

Podcasters discussing the potentional of MAGIC knockdown technique.

TraPS-VarI: Identifying Genetic Variants Altering Phosphotyrosine Signaling Motifs

Podcasters exploring key findings uncovered using TraPS-VarI tool.

STAT3-enhancing Germline Receptor Variants
(STAT3-eGRVs)

Podcasters explain STAT3-eGRVs & significance.