Michael M. Email & Phone Number

Evanston, Il, Us

Burr Ridge, Il, Us

Double Helix Law focuses on biotechnology patent prosecution and I am involved in all aspects of drafting and prosecuting applications at the USPTO and patent offices around the world. In addition to patent prosecution, I have performed freedom-to-operate and patentability searches and evaluated complicated patent portfolios from both an offensive and a defensive mindset. I have also done in-depth prior art searches in support of patent litigation for clients.

Austin, Tx, Us

The research I performed while I was a Graduate Research Assistant suggested the serine/threonine kinase ataxia telangiectasia mutated (ATM) was important for preventing protein aggregation. To visualize the effects of ATM activity on protein aggregation state, I used a combination of immunofluorescence, live-cell imaging, and fluorescence correlation microscopy to compare specific proteins in cells treated with short interfering RNA to ATM or ATM inhibitor. In a separate project, I characterized the cellular effects of expressing ATM alleles with separation-of-function mutations that prevent a specific method of activation. In the canonical pathway, ATM is activated by DNA double-strand breaks while in the more recently discovered pathway, ATM is activated by oxidative stress.

Austin, Tx, Us

DNA double-strand breaks (DSBs) are especially hazardous forms of DNA damage where both strands of DNA are severed at once. DSBs can lead to mutations, chromosomal breaks, and even cell death. As such, there are robust cellular responses, primarily non-homologous end joining and homologous recombination (HR), that rejoin the broken DNA strands. The human protein ataxia telangiectasia mutated (ATM) is a serine/threonine kinase that is activated in the presence of DSBs and the protein complex Mre11/Rad50/Nbs1 (MRN). After activation, ATM phosphorylates hundreds of downstream targets and promotes HR. The MRN complex has multiple enzymatic functions including an ATPase activity in the Rad50 component. Through the use of an ATM mutant that could utilize a bulky ATP analog, I separated the pools of ATP used by MRN and ATM. In vitro kinase assays with purified proteins showed ATP binding by MRN, but not hydrolysis, was required for the activation of ATM. This agrees with the model where the ATPase activity of Rad50 causes conformational changes in the MRN complex that regulate its other functions. In addition to DSB activation, ATM is also activated by oxidative stress in the absence of DSBs. In my other project, I examined the proteomes and phosphoproteomes of cells expressing separation-of-function alleles of ATM that prevent its activation by either oxidative stress or DSBs. Bioinformatic analysis suggested mutations preventing the activation of ATM by either pathway caused increased aggregation in a large portion of the proteome. Further experiments showed multiple proteins were highly aggregated in the absence of ATM kinase activity. In the phosphoproteome of these cells, expression of ATM insensitive to oxidative stress caused changes beyond ATM substrates, demonstrating a robust effect of this kinase in cellular homeostasis, even in the absence of stress.

In this law office focusing on patent prosecution, I gained valuable experience in the varied duties associated with patent prosecution. I went from preparing sequence listings and information disclosure statements to drafting patent applications and responses to Office Actions. While working here, I was involved in more than 20 patent applications in diverse fields, including the biotechnological, pharmaceutical, chemical, and mechanical fields.

Chicago, Il, Us

Patients with chronic myelogenous leukemia (CML) have a translocation between chromosomes 9 and 22 that results in the fusion gene BCR-ABL1. In normal cells, ABL1 has tyrosine kinase activity that is regulated in response to various cellular signals including growth factors. However, the expressed fusion protein BCR-ABL1 has constitutive activity that leads to increased cellular division. Researchers had previously identified a tyrosine kinase inhibitor, Gleevec, that inhibited BCR-ABL1 and was able to inhibit progression of CML in most patients. However, certain mutations in ABL1 render Gleevec ineffective and can trigger a relapse or prevent the initial patient response, necessitating the development of new types of inhibitors. In this lab, I helped develop a high-throughput assay to measure the kinase activity of recombinant ABL1 or BCR-ABL1 present in lysates. This method could be used to screen chemical libraries for novel inhibitors or to assay other kinases with different peptide substrates. I also generated a method for treating and lysing suspension cells in 96-well filter plates to assay hits from high-throughput screens in a cellular environment. In combination, these methods could greatly accelerate the development of new inhibitors for patients with CML.

Bloomington, Indiana, Us

Cancer relapse due to acquired drug resistance is a common problem during treatment. In addition to genetic mutations, epigenetic modifications can also drive increased drug tolerance. Some epigenetic modifications such as cytosine methylation and histone deacetylation decrease the expression of nearby genes and, depending on the gene, can result in dramatic cellular effects. In the Nephew lab, I performed complementary lines of research in ovarian cancer cells. First, I examined how the methylation of cytosine residues changes during the development of drug resistance and second, I determined whether an epigenetic modifier could resensitize cells to a common chemotherapy. For the first aim, I compared changes in the methylation of cytosine residues globally and at specific genes during the acquisition of cisplatin resistance in ovarian cancer cells. The cisplatin-sensitive ovarian cancer cell line A2780 was sequentially treated with increasing doses of cisplatin. The cells from each round had a higher resistance to cisplatin and showed increased levels of methylated cytosine at specific sites throughout the genome. In cells with increased resistance, pathway analysis revealed hypermethylation, and decreased expression, of genes from pathways involved in cell adhesion and tight junctions and hypomethylation, and increased expression, of genes from cell growth promoting pathways. For the second aim, I characterized the histone deacetylase inhibitor OSU-HDAC42 in ovarian cancer cell lines. This drug showed efficacy by itself and was also able to resensitize these cells to cisplatin, the chemotherapy drug frequently used for ovarian cancer. This compound, now known as AR-42, is currently undergoing clinical trials by Arno Therapeutics for the treatment of hematological malignancies and solid tumors.

Doctor Of Law - Jd

Ph.D., Cellular And Molecular Biology

B.S., Biology With Minors In Chemistry, Mathematics, And Psychology