Alberts Laboratory


Our preclinical modeling programs are devoted to understanding how Rho small GTP-binding proteins and their Diaphanous-related formin effectors contribute to responses to chemotherapy in the treatment of solid tumors such as colorectal cancer and myelodysplastic syndromes (MDS), a set of blood neoplasms that can progress to leukemia.


Survivors of all types of cancers now enjoy longer life spans, but the derivative effects of random mutagenesis from therapy can lead to secondary cancers and pre-cancers such as myelodysplasia. Cell structure biogenesis and maintenance studies will address significant questions regarding how cells protect against cancer initiation/development and react to chemo- or radiotherapy.

Our data argues that the mammalian Diaphanous-related formin mDia1 harbors tumor suppressor activity. Genetic studies show that mDia1 loss-of-function is sufficient to impair blood cell development and alters their structure and function—both properties of myelodysplastic syndromes (MDS).

The gene for mDia1, DIAPH1, resides on chromosome 5q in an area where cytogenetic defects frequently occur in MDS and acute myeloid leukemia. A second gene on this chromosome is the familial colon cancer gene APC1. In collaboration with Dr. Gregg Gundersen’s lab at Columbia University, we discovered that mDia1 and APC collaborate in cell structure assembly. Projects in the lab are devoted to creating knowledge of how mDia1 and APC collaborate in tumor suppression.


The discovery and characterization of the molecular mechanism of formin regulation has led us to discover chemical tools to induce Diaphanous-related formin activity to suppress tumorigenesis. Our goal is to translate these chemicals to treat solid tumors and cancers of the blood alone, or as adjuvants for traditional radio- and chemotherapy. There are several reasons to pursue this.

Our collaboration with Dr. George Prendergast’s lab at the Lankenau Medical Research Institute led us to show that formins are required for tumoricidal activity downstream of their activator RhoB. Consistent with this idea, we now know that loss of RhoB function compounds the effects mDia1 knockout to accelerate the progression of MDS.

Our goal now is to pharmacologically develop our formin-activating intramimics as anti-neoplastic agents or as immunomodulating agents to prevent and impair disease acquisition and progression.