Bio sketch Prof. Dr. Ramanjaneyulu Allam
Dr. Allam received PhD in Human biology at University of Munich in 2010, under the supervision of Prof. Hans-Joachim Anders. In 2010, he joined the group of Prof. Jürg Tschopp at university of Lausanne as a postdoctoral fellow, and worked on molecular mechanisms of inflammasome activation. In 2014, he joined the group of Prof. Anne Angelillo-Scherrer at Inselspital, university of Bern as a senior postdoc. Thanks to the award of a Swiss National Science Foundation professorship in 2015, he established his independent research group at Inselspital, University Bern.
Contribution to science
As a graduate student, Dr. Allam characterized the recognition of nucleic acids by the innate immune system in the context of auto-immunity. He also found a role for murine double minute (Mdm)-2 in systemic lupus erythematosus (SLE). Later he focused on exogenous and endogenous molecules that activate innate immunity. In this context, he identified histones as danger-associated molecular patterns that activate toll like receptors 2 and 4, and NLRP3 inflammasome. He also found that antibiotics activate the NLRP3 inflammasome, a cytosolic innate immune sensor. During his postdoctoral research in the field of inflammasomes with late Prof. Jürg Tschopp in Lausanne, he worked on understanding the molecular mechanism of inflammasomes. Initially, he was involved in understanding the mechanism of inhibitor of apoptosis proteins (IAP) induced inflammasome activation. Further, he also characterized the role of mitochondrial-dependent apoptosis in NLRP3 inflammasome activation and involved in deciphering the role of NAIP in colonic tumorigenesis. After establishing his independent research group his team unravelled novel in vivo role for higher vertebrate specific protein Ribonuclease inhibitor (RNH1) in erythropoiesis. His group found that RNH1 is a ribosomal associated protein, it binds to ribosomes and regulates erythropoiesis by regulating the translation of erythroid specific transcription factor GATA1.
Major achievements of the last 5 years
- Dr. Allam received SNSF professorship
- Dr. Allam received Johanna Dürmüller-Bol DBMR Research Prize
- Dr. Allam ASH abstract achievement award
- Lab member Mrs. Martina Stilinovic received best preclinical project poster prize of the DBMR.
- Lab member Mrs. Martina Stilinovic received ISEH travel grant.
- Lab member Mr. Giuseppe Bombaci is awarded PhD for his thesis from GCB, University Bern
Understand the role of RNH1 in Haematopoiesis, Translation and Inflammation
Ribonuclease Inhibitor (RNH1) or Ribonuclease/Angiogenin Inhibitor is a higher-vertebrate specific protein and contains leucine-rich repeat (LRR). It binds to and inhibits ribonucleases such as RNase A, RNase 1, eosinophil-derived neurotoxin (EDN, also known as RNase 2) and RNase 4. We recently published that RNH1 is a novel ribosomal associated protein, it binds to ribosomes and regulates erythropoiesis by regulating the translation of erythroid specific transcription factor GATA1.These findings reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis (JCI, 2018). Currently, we are interested in understanding the molecular mechanism of RNH1 in translation and Haematopoiesis. Interestingly, the LRRs of RNH1 are very similar to those of NLRP proteins. NLRP proteins belong to NOD-like receptors (NLRs) family and form inflammasome complexes. So, we are also investigating the role of RNH1 in Inflammation.
The fundamental aspects of this research will provide a better understanding of the RNH1 in haematopoies and inflammation. In addition, such knowledge could establish the molecular basis for the development of novel therapeutic strategies for inflammatory and hematopoietic disorders.
Investigating the role of Inflammasomes in myeloid malignancies
Myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are heterogeneous disorders derived from myeloid stem and progenitor bone marrow cells. Genetically, they are very heterogeneous and characterized by uncontrolled proliferation and/or blockage of differentiation of abnormal myeloid progenitor cells. Our understanding of the genetic causes of these diseases has improved during the past decade by the identification of multiple driving somatic mutations and epigenetic alterations in MDS and AML patients. However, due to multiple interactions and the heterogeneity of the mutational landscape, the detailed pathophysiological mechanisms leading to MDS and progression to AML are still not fully understood. We are investigating the role and molecular mechanism of inflammasomes in myeloid malignancies.
List of collaborators
- Prof. Fabio Martinon (Department of Biochemistry-University of Lausanne)
- Prof. Pascal Schneider (Department of Biochemistry-University of Lausanne)
- Prof. Anne Angelillo-Scherrer (Klinik für Hämatologie und Hämatologisches Zentrallabor, Inselspital, Bern)
- Prof. Trang Hoang, University of Montreal (CA)
- Prof. Vijay Sankaran, Harvard Medical School(USA)
We are extremely grateful for all the sources that have funded our research.
- Swiss national science foundation (SNSF)
- Krebsforschung Schweiz
- Novartis research foundation
- Olga Mayenfisch Stiftung